Materiały źródłowe

• #1 pathogenesis of Pre eclampsia | PPT

  https://www.slideshare.net/slideshow/pathogenesis-of-pre-eclampsia/100915337

  Preeclampsia is a disorder that is unique to human pregnancy, and the only known cure for this complication is delivery. […] Preeclampsia affects approximately 4% to 5% of pregnancies. […] The Preeclampsia Foundation states that: Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. […] As is evident from the statement that, preeclampsia is a major contributor to maternal and fetal morbidity and mortality worldwide. […] In India, the incidence of preeclampsia is reported to be 8-10% among the pregnant women. […] According to a study, the prevalence of hypertensive disorders of pregnancy was 7.8% with preeclampsia in 5.4% of the study population in India. […] Preeclampsia is a disease Hypertensive Disorder in Pregnancy Pregnancy induced hypertension Gestational hypertension w/o proteinuria Preeclampsia (PIH + proteinuria) Eclampsia (PIH + convulsions) HELLP syndrome Pre-existing hypertension (chronic hypertension) Preeclampsia syndrome superimposed on chronic hypertension Unclassified hypertension.

• #2 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Preeclampsia is a serious complication of pregnancy where it affects 5–8% of all pregnancies. […] Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. […] The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. […] At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. […] Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. […] Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension.

• #3 Preeclampsia: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-pathogenesis

  Preeclampsia is a pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria after 20 weeks of gestation. […] The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which leads to the progressive release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause hypertension, vasospasm, platelet aggregation, and the other manifestations of the disease. […] However, the trigger for abnormal placental development and the subsequent cascade of events remains unknown.

• #4 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  The pathogenesis of pre-eclampsia can be considered to involve two stages: abnormal placentation and the development of the maternal syndrome. Genetic factors, maternal factors and immunological factors may cause placental dysfunction (stage I), which in turn leads to the release of antiangiogenic factors (such as soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sENG)) and other inflammatory mediators that induce preeclampsia (stage II). […] Pre-eclampsia is understood to originate in the placenta, and its initial stages can be understood as the placental syndrome. The presence of the placenta, as opposed to the fetus, is essential to the development of pre-eclampsia, which is evident by the development of the condition in hydatidiform mole. […] The characteristics of pre-eclamptic placenta have been studied for well over a century.

• #5 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Preeclampsia is a serious complication of pregnancy and complicates its course in 2-8% of all cases. […] Of particular interest is the study of the molecular mechanisms of etiopathogenesis and risk factors for preeclampsia, which, unfortunately, are currently poorly studied and understood, thus dictating the need for further study of this complication of pregnancy. […] This article discusses the current understanding of the etiology, pathogenesis and risk factors for preeclampsia. […] The mechanisms of PE occurrence are extensively studied worldwide, and 30 hypotheses for the development of this pregnancy complication were reported, most of which placentation disorders are the most significant. […] The two-stage model of PE development that was introduced by Redman in 1991 is currently generally accepted. At stage 1 of PE, abnormal placentation occurs in early pregnancy, which leads to disseminated endothelial dysfunction and maternal syndrome at stage 2.

• #6 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  The pathogenesis of pre-eclampsia can be considered to involve two stages: abnormal placentation and the development of the maternal syndrome. Genetic factors, maternal factors and immunological factors may cause placental dysfunction (stage I), which in turn leads to the release of antiangiogenic factors (such as soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sENG)) and other inflammatory mediators that induce preeclampsia (stage II). […] Pre-eclampsia is understood to originate in the placenta, and its initial stages can be understood as the placental syndrome. The presence of the placenta, as opposed to the fetus, is essential to the development of pre-eclampsia, which is evident by the development of the condition in hydatidiform mole. […] The characteristics of pre-eclamptic placenta have been studied for well over a century.

• #7 Preeclampsia: Pathophysiology and the Maternal-Fetal Risk

  https://clinmedjournals.org/articles/jhm/journal-of-hypertension-and-management-jhm-3-024.php?jid=jhm

  Preeclampsia is primarily a disease of the placenta as it may be encountered in molar pregnancies. […] One of the most accepted theories in preeclampsia revolves around abnormal placentation. In normal pregnancies, trophoblast begins invasion into the myometrial blood vessels by remodeling the maternal spiral arteries, transforming them from small, muscular, higher resistance arterioles into large caliber arteries with high capacitance and free flow of blood. […] Failure of this process of complete remodeling leads to persistence of high resistance spiral arteries that impede placental perfusion thereby leading to a state of „relative hypoxemia” which culminates into maternal endothelial cell dysfunction. […] Maternal systemic endothelial cell dysfunction manifests in signs and symptoms that are reflective of maternal vasoconstriction and multi-organ damage outlined in Table 1.

• #8 Hypertensive Disorders of Pregnancy – OpenAnesthesia

  https://www.openanesthesia.org/keywords/hypertensive-disorders-of-pregnancy/

  The pathogenesis of preeclampsia is abnormal placentation due to impaired angiogenesis of spiral arteries (terminal branches of the uterine artery), leading to placental ischemia and release of antiangiogenic factors to maternal circulation, leading to systemic endothelial dysfunction. […] During normal placental development, fetal cytotrophoblasts invade the maternal spiral arteries, converting them into large caliber capacitance vessels capable of providing adequate placental perfusion to sustain fetal growth. […] In preeclampsia, the fetal cytotrophoblasts fail to differentiate into the invasive endothelial phenotype. […] The end result is a shallow invasion of the maternal spiral arteries, which remain small-caliber, high-resistance vessels. […] This results in relative placental under perfusion, hypoxia, oxidative stress, and release of antiangiogenic factors into the maternal circulation, causing widespread systemic maternal endothelial dysfunction.

• #9 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  In pre-eclampsia, the physiological changes of the spiral arteries were restricted to the decidua, whereas in normal pregnancy they extended proximally into the myometrium. […] Molecular mechanisms that mediate spiral artery remodelling are still being debated. […] The concept of defective placentation and failure to transform uterine spiral arteries has emerged as central to the pathogenesis of pre-eclampsia. […] Oxidative stress also occurs at the maternalfetal interface and is thought to have a key role in normal and defective placental development. […] The haem oxygenase (HO) pathway is an important mediator of oxidative stress. […] Endoplasmic reticulum (ER) stress has also been reported in the placental tissue obtained from patients with pre-eclampsia. […] Elucidating the underlying cause of defective placentation warrants an understanding of the immunological tolerance that is required at the maternalplacental interface.

• #10 Hypertensive Disorders of Pregnancy – OpenAnesthesia

  https://www.openanesthesia.org/keywords/hypertensive-disorders-of-pregnancy/

  The pathogenesis of preeclampsia is abnormal placentation due to impaired angiogenesis of spiral arteries (terminal branches of the uterine artery), leading to placental ischemia and release of antiangiogenic factors to maternal circulation, leading to systemic endothelial dysfunction. […] During normal placental development, fetal cytotrophoblasts invade the maternal spiral arteries, converting them into large caliber capacitance vessels capable of providing adequate placental perfusion to sustain fetal growth. […] In preeclampsia, the fetal cytotrophoblasts fail to differentiate into the invasive endothelial phenotype. […] The end result is a shallow invasion of the maternal spiral arteries, which remain small-caliber, high-resistance vessels. […] This results in relative placental under perfusion, hypoxia, oxidative stress, and release of antiangiogenic factors into the maternal circulation, causing widespread systemic maternal endothelial dysfunction.

• #11 Hypertensive Disorders of Pregnancy – OpenAnesthesia

  https://www.openanesthesia.org/keywords/hypertensive-disorders-of-pregnancy/

  The pathogenesis of preeclampsia is abnormal placentation due to impaired angiogenesis of spiral arteries (terminal branches of the uterine artery), leading to placental ischemia and release of antiangiogenic factors to maternal circulation, leading to systemic endothelial dysfunction. […] During normal placental development, fetal cytotrophoblasts invade the maternal spiral arteries, converting them into large caliber capacitance vessels capable of providing adequate placental perfusion to sustain fetal growth. […] In preeclampsia, the fetal cytotrophoblasts fail to differentiate into the invasive endothelial phenotype. […] The end result is a shallow invasion of the maternal spiral arteries, which remain small-caliber, high-resistance vessels. […] This results in relative placental under perfusion, hypoxia, oxidative stress, and release of antiangiogenic factors into the maternal circulation, causing widespread systemic maternal endothelial dysfunction.

• #12 Hypertensive Disorders of Pregnancy – OpenAnesthesia

  https://www.openanesthesia.org/keywords/hypertensive-disorders-of-pregnancy/

  The pathogenesis of preeclampsia is abnormal placentation due to impaired angiogenesis of spiral arteries (terminal branches of the uterine artery), leading to placental ischemia and release of antiangiogenic factors to maternal circulation, leading to systemic endothelial dysfunction. […] During normal placental development, fetal cytotrophoblasts invade the maternal spiral arteries, converting them into large caliber capacitance vessels capable of providing adequate placental perfusion to sustain fetal growth. […] In preeclampsia, the fetal cytotrophoblasts fail to differentiate into the invasive endothelial phenotype. […] The end result is a shallow invasion of the maternal spiral arteries, which remain small-caliber, high-resistance vessels. […] This results in relative placental under perfusion, hypoxia, oxidative stress, and release of antiangiogenic factors into the maternal circulation, causing widespread systemic maternal endothelial dysfunction.

• #13 Pre-eclampsia: its pathogenesis and pathophysiolgy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4928171/

  Pre-eclampsia is a pregnancy-specific disorder that has a worldwide prevalence of 58%. […] Recently it has been postulated that it is a two-stage disease with an imbalance between angiogenic and anti-antigenic factors. […] The central hypothesis is that pre-eclampsia results from defective spiral artery remodelling, leading to cellular ischaemia in the placenta, which in turn results in an imbalance between anti-angiogenic and pro-angiogenic factors. […] The main pathological feature of early-onset PE is incomplete transformation of the spiral arteries, resulting in hypoperfusion of the placenta and reduced nutrient supply to the foetus. […] In PE, it has almost been established that there is reduced blood flow to the placenta, especially in the early-onset type, because of defective spiral artery remodelling and acute artherosis.

• #14 Preeclampsia: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-pathogenesis

  Preeclampsia is a pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria after 20 weeks of gestation. […] The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which leads to the progressive release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause hypertension, vasospasm, platelet aggregation, and the other manifestations of the disease. […] However, the trigger for abnormal placental development and the subsequent cascade of events remains unknown.

• #15 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  The endothelial cell dysfunction that is characteristic of preeclampsia may be partially due to an extreme activation of leukocytes in the maternal circulation, as evidenced by an upregulation of type 1 helper T cells. […] Placental implantation with abnormal trophoblastic invasion of uterine vessels is a major cause of hypertension associated with preeclampsia syndrome. In fact, studies have shown that the degree of incomplete trophoblastic invasion of the spiral arteries is directly correlated with the severity of subsequent maternal hypertension. This is because the placental hypoperfusion resulting from the incomplete invasion leads by an unclear pathway to the release of systemic vasoactive compounds that cause an exaggerated inflammatory response, vasoconstriction, endothelial damage, capillary leak, hypercoagulability, and platelet dysfunction, all of which contribute to organ dysfunction and the various clinical features of the disease.

• #16 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  Preeclampsia (PE) is defined as new onset hypertension after 20 weeks of gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. […] Toxic substances that damage the maternal vascular endothelium induce PE, resulting in liver and kidney malfunction. […] VEGF, sFlt1, sENG, PAPP-A, inhibin A and activin A proteins, fetal hemoglobin, heat shock protein and placental protein have been helpful in predicting or diagnosing PE and in understanding its pathogenesis. […] The pathogenesis of PE is unknown. Currently PE is commonly thought to be a two-stage disease. The first stage is reduced placental perfusion, caused by abnormal implantation and placental vascular development, due to an imbalance in angiogenic factors. The second stage of PE, maternal response, is manifested by widespread inflammation and maternal endothelian cell dysfunction, increased markers of oxidative stress, insulin resistance, reduced immune function and dyslipidemia.

• #17 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  The hallmarks of pre-eclampsia are not confined to the placenta but also extend to widespread effects in the mother that can be collectively viewed as the maternal syndrome. […] Experimental and epidemiological studies support a pathological role for imbalance in circulating angiogenic factors in the aetiology of the maternal syndrome. Excess levels of the antiangiogenic factor sFLT1, which is produced in the placenta and released into the maternal circulation, induce maternal endothelial dysfunction leading to preeclamptic signs and symptoms. […] High levels of antiangiogenic factors and low levels of proangiogenic factors are useful biomarkers for the early detection and prognosis of pre-eclampsia; these markers also serve as theranostics in clinical trials.

• #18 Pre-eclampsia | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-023-00417-6

  Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. […] Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. […] Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. […] Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

• #19 Preeclampsia: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-pathogenesis

  Preeclampsia is a pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria after 20 weeks of gestation. […] The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which leads to the progressive release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause hypertension, vasospasm, platelet aggregation, and the other manifestations of the disease. […] However, the trigger for abnormal placental development and the subsequent cascade of events remains unknown.

• #20 Preeclampsia: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-pathogenesis

  Preeclampsia is a pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria after 20 weeks of gestation. […] The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which leads to the progressive release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause hypertension, vasospasm, platelet aggregation, and the other manifestations of the disease. […] However, the trigger for abnormal placental development and the subsequent cascade of events remains unknown.

• #21 Pre-eclampsia: its pathogenesis and pathophysiolgy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4928171/

  The exact mechanism for this is not known but various factors, such as abnormal genetic variations, biology of the trophoblasts or defective trophoblast differentiation acting together with extrinsic factors, such as maternal constitutional factors, action of macrophage defense mechanisms, impaired action of dNK cells and maternal endothelial cells have been advanced. […] It is therefore believed that placental ischaemiareperfusion injury is central to the development of PE. […] There is increasing evidence that suggests an imbalance between pro-angiogenic and anti-angiogenic factors are responsible for the pathophysiological effects seen in PE, and these appear before clinical signs are apparent. […] The disproportionate levels of anti-angiogenic factors such as sEng and sFlt-1, and pro-angiogenic factors such as VEGF, PlGF and TGF, are believed to cause generalised maternal endothelial dysfunctions, leading to hypertension, renal endotheliosis and blood coagulation.

• #22 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  The hallmarks of pre-eclampsia are not confined to the placenta but also extend to widespread effects in the mother that can be collectively viewed as the maternal syndrome. […] Experimental and epidemiological studies support a pathological role for imbalance in circulating angiogenic factors in the aetiology of the maternal syndrome. Excess levels of the antiangiogenic factor sFLT1, which is produced in the placenta and released into the maternal circulation, induce maternal endothelial dysfunction leading to preeclamptic signs and symptoms. […] High levels of antiangiogenic factors and low levels of proangiogenic factors are useful biomarkers for the early detection and prognosis of pre-eclampsia; these markers also serve as theranostics in clinical trials.

• #23 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-eclampsia. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. […] The past two decades have seen major advances in the field of pre-eclampsia, although the underlying pathogenesis remains elusive. Currently, the disease can be understood in terms of both placental and maternal dysfunction. Various genetic, angiogenic, structural and metabolic pathways have been implicated in pre-eclampsia, including spiral artery remodelling, placental oxygenation, redox and immune tolerance at the maternalfetal interface and the balance of angiogenic and antiangiogenic factors. In particular, certain antiangiogenic proteins have emerged as key pathogenic mediators of the maternal disease, and their discovery has provided opportunities for the development of novel diagnostics such as risk calculators, prediction models and triage tools.

• #24 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Excessive production of antiangiogenic sFlt-1 and sEng reduces the bioavailability of free pro-angiogenic PlGF and VEGF, by binding and neutralizes VEGF and PlGF, thus reducing the availability of free VEGF for fetal and placental angiogenesis. […] In comparison, the sEng is implicated in neutralizing TGF- β, an anti-inflammatory growth factor that activates eNOS. […] This imbalance leads to systemic endothelial dysfunction, including in the kidney, where disruption of slit diaphragm was reported, as VEGF is essential for the maintenance glomerular barrier. […] Support for the adverse effect of preeclampsia on glomerular barrier was reported by Henao et al. […] These authors demonstrated that when a human podocyte cell line was stimulated with serum from women with preeclampsia, disruption of CD2AP, podocin and actin were observed, but not when sera from normal pregnancy was added.

• #25 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Pre-eclampsia is thought to result from an abnormal placenta, the removal of which ends the disease in most cases. […] Abnormal development of the placenta leads to poor placental perfusion. The placenta of women with pre-eclampsia is abnormal and characterized by poor trophoblastic invasion. […] It is thought that this results in oxidative stress, hypoxia, and the release of factors that promote endothelial dysfunction, inflammation, and other possible reactions. […] The clinical manifestations of pre-eclampsia are associated with general endothelial dysfunction, including vasoconstriction and end-organ ischemia. […] Implicit in this generalized endothelial dysfunction may be an imbalance of angiogenic and anti-angiogenic factors. […] Both circulating and placental levels of soluble fms-like tyrosine kinase-1 (sFlt-1) are higher in women with pre-eclampsia than in women with normal pregnancy.

• #26 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Excessive production of antiangiogenic sFlt-1 and sEng reduces the bioavailability of free pro-angiogenic PlGF and VEGF, by binding and neutralizes VEGF and PlGF, thus reducing the availability of free VEGF for fetal and placental angiogenesis. […] In comparison, the sEng is implicated in neutralizing TGF- β, an anti-inflammatory growth factor that activates eNOS. […] This imbalance leads to systemic endothelial dysfunction, including in the kidney, where disruption of slit diaphragm was reported, as VEGF is essential for the maintenance glomerular barrier. […] Support for the adverse effect of preeclampsia on glomerular barrier was reported by Henao et al. […] These authors demonstrated that when a human podocyte cell line was stimulated with serum from women with preeclampsia, disruption of CD2AP, podocin and actin were observed, but not when sera from normal pregnancy was added.

• #27 Pre-eclampsia | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-023-00417-6

  Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. […] Soluble endoglin contributes to the pathogenesis of preeclampsia. […] The role of angiogenic factors in the management of preeclampsia. […] The role of inflammation in the pathogenesis of preeclampsia. […] Recent insights into the pathophysiology of preeclampsia.

• #28

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  However, the precise cause for both deficient spiral artery remodeling and its effects on the development of hypertension remain unclear. […] Placental ischemia is thought to cause hypoxia-induced release of placental factors, leading to widespread vascular and endothelial dysfunction. Endothelial dysfunction, which is associated with the development of hypertension, occurs due to an imbalance in angiogenic factors. […] Thus angiogenic factors have drawn increasing attention for their role in the pathogenesis of preeclampsia. […] Preeclampsia is characterized by an excess of anti-angiogenic factors with a simultaneous deficiency in pro-angiogenic factors. […] sFlt-1 appears to enact its anti-angiogenic effects through the antagonism of VEGF and PlGF. […] This effect of sFlt-1 is dose-dependent fashion, with a strong correlation of sFlt level and severity of disease.

• #29 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  A pro-oxidant-antioxidant imbalance favours oxidation, which results in oxidative stress (OS). However, uncontrolled lipid peroxidation can occur in PE, impairing normal endothelial cell function. […] Numerous molecules govern the processes of angiogenesis and vascular homeostasis. The VEGF (vascular endothelial growth factor), PlGF (placental growth factor), soluble fms-like tyrosine kinase (sFlt1) and soluble endoglin (sEng) have all been related to the pathophysiology of PE in humans. […] The link between elevated sFlt-1 and PE has been shown in several studies. Levels of sFlt-1 are strongly linked to illness severity, hypertension, and proteinuria. […] The presence of several protein biomarkers is associated with PE. The following proteins help predict or diagnose PE and aid in the understanding of its pathogenesis: VEGF, sFlt1, sENG, PAPP-A, inhibin A, activin A, fetal hemoglobin, heat shock protein and PP13.

• #30

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  However, the precise cause for both deficient spiral artery remodeling and its effects on the development of hypertension remain unclear. […] Placental ischemia is thought to cause hypoxia-induced release of placental factors, leading to widespread vascular and endothelial dysfunction. Endothelial dysfunction, which is associated with the development of hypertension, occurs due to an imbalance in angiogenic factors. […] Thus angiogenic factors have drawn increasing attention for their role in the pathogenesis of preeclampsia. […] Preeclampsia is characterized by an excess of anti-angiogenic factors with a simultaneous deficiency in pro-angiogenic factors. […] sFlt-1 appears to enact its anti-angiogenic effects through the antagonism of VEGF and PlGF. […] This effect of sFlt-1 is dose-dependent fashion, with a strong correlation of sFlt level and severity of disease.

• #31 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Oxidative damage to the placenta induces apoptosis processes, such as the release of various antiangiogenic factors, proinflammatory cytokines, and vasoactive compounds into the mothers bloodstream, which develops major systemic endothelial cell dysfunction, accompanied by inflammation and vasoconstriction. […] Endothelial dysfunction is central to the maternal syndrome pathogenesis of PE and underlies the imbalance of vasoactive mediators, which induces a shift toward increased vasoconstrictor production. […] An endogenous antiangiogenic factor (endostatin), sFlt1, is a potent VEGF antagonist that is significantly elevated in PE. […] Increased expression of sFlt1 (in vitro) induces glomerular endotheliosis with the disappearance of fenestras, which histologically resembles renal damage in PE.

• #32 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Excessive production of antiangiogenic sFlt-1 and sEng reduces the bioavailability of free pro-angiogenic PlGF and VEGF, by binding and neutralizes VEGF and PlGF, thus reducing the availability of free VEGF for fetal and placental angiogenesis. […] In comparison, the sEng is implicated in neutralizing TGF- β, an anti-inflammatory growth factor that activates eNOS. […] This imbalance leads to systemic endothelial dysfunction, including in the kidney, where disruption of slit diaphragm was reported, as VEGF is essential for the maintenance glomerular barrier. […] Support for the adverse effect of preeclampsia on glomerular barrier was reported by Henao et al. […] These authors demonstrated that when a human podocyte cell line was stimulated with serum from women with preeclampsia, disruption of CD2AP, podocin and actin were observed, but not when sera from normal pregnancy was added.

• #33 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  This concept is supported by the observation that bevacizumab, an anti-VEGF antibody used to treat patients with various types of cancer or diabetic proliferative retinopathy causes hypertension and proteinuria mimicking the effect of sFlt-1. […] Kidney damage during preeclampsia as evident by endothelial and podocytes’ loss contributes to the increased risk of later hypertension, CKD, ischemic heart disease, stroke, persistent proteinuria and finally ends stage renal disease (ESRD). […] As mentioned above, superficial placental implantation due to abnormal angiogenesis is the early driving event for the development of preeclampsia. […] The imbalance between the pro-angiogenic VEGF and PlGF, and the antiangiogenic sFlt-1 and sEng plays a central role in the pathogenesis of placental hypoxia, as both VEGF and PlGF are essential for fetal and placental angiogenesis.

• #34 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  Data show that an imbalance of proangiogenic and antiangiogenic factors produced by the placenta may play a major role in mediating endothelial dysfunction. Angiogenesis is critical for successful placentation and the normal interaction between trophoblasts and endothelium. […] Evidence also suggests that oxidative stress, circulatory maladaptation, inflammation, and humoral, mineral, and metabolic abnormalities contribute to the endothelial dysfunction and pathogenesis of preeclampsia.

• #35 Pre-eclampsia: its pathogenesis and pathophysiolgy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4928171/

  The exact mechanism for this is not known but various factors, such as abnormal genetic variations, biology of the trophoblasts or defective trophoblast differentiation acting together with extrinsic factors, such as maternal constitutional factors, action of macrophage defense mechanisms, impaired action of dNK cells and maternal endothelial cells have been advanced. […] It is therefore believed that placental ischaemiareperfusion injury is central to the development of PE. […] There is increasing evidence that suggests an imbalance between pro-angiogenic and anti-angiogenic factors are responsible for the pathophysiological effects seen in PE, and these appear before clinical signs are apparent. […] The disproportionate levels of anti-angiogenic factors such as sEng and sFlt-1, and pro-angiogenic factors such as VEGF, PlGF and TGF, are believed to cause generalised maternal endothelial dysfunctions, leading to hypertension, renal endotheliosis and blood coagulation.

• #36 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  In pre-eclampsia, the physiological changes of the spiral arteries were restricted to the decidua, whereas in normal pregnancy they extended proximally into the myometrium. […] Molecular mechanisms that mediate spiral artery remodelling are still being debated. […] The concept of defective placentation and failure to transform uterine spiral arteries has emerged as central to the pathogenesis of pre-eclampsia. […] Oxidative stress also occurs at the maternalfetal interface and is thought to have a key role in normal and defective placental development. […] The haem oxygenase (HO) pathway is an important mediator of oxidative stress. […] Endoplasmic reticulum (ER) stress has also been reported in the placental tissue obtained from patients with pre-eclampsia. […] Elucidating the underlying cause of defective placentation warrants an understanding of the immunological tolerance that is required at the maternalplacental interface.

• #37 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #38 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  In preeclampsia, ROS are produced in poorly perfused placentas, inducing vasoconstriction and resulting in endothelial dysfunction. […] An imbalance between ROS and NO levels is thought to contribute to vasodilatory dysfunction in preeclampsia. […] Hypoxia is necessary for the invasion of EVTs into the uterine decidua and myometrium. […] HIF-1 is stimulated by oxidative stress and growth factors to induce glycolytic activity. […] The abnormal protein reaction under hypoxic conditions could contribute to the pathogenesis of preeclampsia. […] HIF is also critical for EVT invasion into the maternal uterine decidua and myometrium during placentation. […] Disturbed placental angiogenesis impairs placental perfusion, leading to the production of abundant soluble vascular endothelial growth factor receptor-1 (sFlt-1) and soluble endoglin (sEng), and reduces the production of placental growth factor (PlGF), which appears in the maternal circulation several weeks before the onset of preeclampsia.

• #39 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  A pro-oxidant-antioxidant imbalance favours oxidation, which results in oxidative stress (OS). However, uncontrolled lipid peroxidation can occur in PE, impairing normal endothelial cell function. […] Numerous molecules govern the processes of angiogenesis and vascular homeostasis. The VEGF (vascular endothelial growth factor), PlGF (placental growth factor), soluble fms-like tyrosine kinase (sFlt1) and soluble endoglin (sEng) have all been related to the pathophysiology of PE in humans. […] The link between elevated sFlt-1 and PE has been shown in several studies. Levels of sFlt-1 are strongly linked to illness severity, hypertension, and proteinuria. […] The presence of several protein biomarkers is associated with PE. The following proteins help predict or diagnose PE and aid in the understanding of its pathogenesis: VEGF, sFlt1, sENG, PAPP-A, inhibin A, activin A, fetal hemoglobin, heat shock protein and PP13.

• #40 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  A pro-oxidant-antioxidant imbalance favours oxidation, which results in oxidative stress (OS). However, uncontrolled lipid peroxidation can occur in PE, impairing normal endothelial cell function. […] Numerous molecules govern the processes of angiogenesis and vascular homeostasis. The VEGF (vascular endothelial growth factor), PlGF (placental growth factor), soluble fms-like tyrosine kinase (sFlt1) and soluble endoglin (sEng) have all been related to the pathophysiology of PE in humans. […] The link between elevated sFlt-1 and PE has been shown in several studies. Levels of sFlt-1 are strongly linked to illness severity, hypertension, and proteinuria. […] The presence of several protein biomarkers is associated with PE. The following proteins help predict or diagnose PE and aid in the understanding of its pathogenesis: VEGF, sFlt1, sENG, PAPP-A, inhibin A, activin A, fetal hemoglobin, heat shock protein and PP13.

• #41 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  The maternal immune system fails to adequately tolerate fetal antigens, leading to an imbalance in immune cells (natural killer (NK) cells and regulatory T cells (Tregs)) and resulting in inflammatory responses and inadequate spiral artery remodeling. […] The genetic and epigenetic hypothesis focuses on genetic predispositions and epigenetic changes, suggesting that genetic variants in both the mother and fetus affect placental development, while epigenetic modifications (DNA methylation, histone modification) influence gene expression related to immune response and angiogenesis. […] The hypoxic placenta generates excess ROS, such as superoxide anion (O2−) and hydrogen peroxide (H2O2), primarily through the activities of NADPH oxidase and xanthine oxidase (XO). […] Elevated levels of serum uric acid, a byproduct of XO activity, are commonly observed in PE. This hyperuricemia, particularly when adjusted for serum creatinine (SUA/sCr), is a significant marker of oxidative stress and vascular dysfunction. Increased XO activity and the resulting oxidative stress are directly linked to the severity of PE and its complications, including hypertension and organ damage.

• #42 Preventing Pre-eclampsia and its Complications | Article | GLOWM

  https://www.glowm.com/article/heading/vol-2–health-and-risk-in-pregnancy-and-childbirth–preventing-preeclampsia-and-its-complications/id/416343

  In pre-eclampsia, it is hypothesized that impaired placentation results in placental ischemia and reperfusion injuries, which in turn cause oxidative stress and the subsequent clinical manifestations of disease. […] In women with pre-eclampsia, there is evidence of oxidative stress in the placenta and maternal circulation with increased production of reactive oxygen species and decreased concentrations of antioxidant defence mechanisms such as vitamins C and E. Antioxidants play an important role in the removal and inactivation of free radicals and other oxidative products, which would otherwise trigger the endothelial dysfunction and end-organ damage in pre-eclampsia. It is therefore hypothesized that treatment with antioxidants such as vitamins C and E may reduce the oxidative stress in pre-eclampsia and thereby reduce the manifestations of disease.

• #43 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  In pre-eclampsia, the physiological changes of the spiral arteries were restricted to the decidua, whereas in normal pregnancy they extended proximally into the myometrium. […] Molecular mechanisms that mediate spiral artery remodelling are still being debated. […] The concept of defective placentation and failure to transform uterine spiral arteries has emerged as central to the pathogenesis of pre-eclampsia. […] Oxidative stress also occurs at the maternalfetal interface and is thought to have a key role in normal and defective placental development. […] The haem oxygenase (HO) pathway is an important mediator of oxidative stress. […] Endoplasmic reticulum (ER) stress has also been reported in the placental tissue obtained from patients with pre-eclampsia. […] Elucidating the underlying cause of defective placentation warrants an understanding of the immunological tolerance that is required at the maternalplacental interface.

• #44

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  CO, a metabolite produced by HO, is known to have vasodilatory properties on placental vasculature, reducing placental perfusion pressure and allowing for increased blood flow. […] Another important factor in preeclampsia is hypoxia-inducible factor 1-alpha (HIF-1), a transcription factor that regulates cell responses to hypoxic environments, such as the ischemic placenta. […] Furthermore, they found that downregulation of HIF-1 in these preeclampsia rat models resulted in a significant reduction in hypertension and proteinuria compared to control rats, thus directly implicating elevated HIF-1 in the pathogenesis of preeclampsia. […] The renin-angiotensin system (RAS) also likely plays a role in preeclampsia. […] This relationship has a dose dependent relationship with levels of AT1-AA positively correlating with the severity of disease.

• #45 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #46 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  The endothelial cell dysfunction that is characteristic of preeclampsia may be partially due to an extreme activation of leukocytes in the maternal circulation, as evidenced by an upregulation of type 1 helper T cells. […] Placental implantation with abnormal trophoblastic invasion of uterine vessels is a major cause of hypertension associated with preeclampsia syndrome. In fact, studies have shown that the degree of incomplete trophoblastic invasion of the spiral arteries is directly correlated with the severity of subsequent maternal hypertension. This is because the placental hypoperfusion resulting from the incomplete invasion leads by an unclear pathway to the release of systemic vasoactive compounds that cause an exaggerated inflammatory response, vasoconstriction, endothelial damage, capillary leak, hypercoagulability, and platelet dysfunction, all of which contribute to organ dysfunction and the various clinical features of the disease.

• #47 Preeclampsia: From Etiopathology to Organ Dysfunction | IntechOpen

  https://www.intechopen.com/chapters/79809

  The severity of the disease correlates with the magnitude of defective trophoblastic invasion. […] In preeclampsia, inflammatory mediators contributed by systemic oxidative stress are tumor necrosis factor alpha (TNF-Alpha) and interleukins that in turn lead to formation of lipid peroxidases, producing toxic radicals that injure systemic vascular endothelial cells. […] Injury to systemic endothelial cell is crucial in pathogenesis of preeclampsia and likely secretes placental protein factors into maternal circulation, which provokes activation and dysfunction of systemic vascular endothelium, producing less nitric oxide contributing to vasoconstriction, and promotes coagulation and greater sensitivity to vasopressors. […] There is an imbalance of proangiogenic (VEGF) and antiangiogenic (soluble fms-like tyrosine kinase sFlt-I) proteins in placental vascular bed. […] In preeclampsia, sFlt-1 is a soluble antiangiogenic protein that is elevated, which binds and inactivates or reduces biological activity of free-circulating proangiogenic proteins, vascular endothelial growth factor (VEGF), and placental growth factor (PIGF), causing endothelial dysfunction.

• #48 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  During normal placental development, extravillous cytotrophoblast invades the decidual and myometrial spiral arteries. These spiral arteries then lose their endothelial nature and transform themselves from high resistance vessels into large vessels capable of providing adequate placental perfusion to supply nourishment to the developing fetus. This results in impaired spiral artery remodeling and relative placental ischemia. A trophoblast defect can cause shallow placentation, placental ischemia, insufficient spiral artery transformation and the maternal syndrome of preeclampsia. […] The NK cells produce angiogenesis-promoting cytokines and proteins but cannot remodel spiral arteries downstream. Furthermore, PE has been shown to activate circulating T and NK cells. […] Hypoxia-inducible factors (HIF) 1 and 2, markers of cellular oxygen deficiency, were detected in high quantities in the placentas of PE patients.

• #49 Eclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/253960-overview

  Many uterovascular changes occur when a woman is pregnant. It is believed that these changes are due to the interaction between fetal and maternal allografts and result in systemic and local vascular changes. It has been shown that in patients with eclampsia, the development of uteroplacental arteries is hindered. […] It is believed that in eclampsia there is abnormal cerebral blood flow in the setting of extreme hypertension. The regulation of cerebral perfusion is inhibited, vessels become dilated with increased permeability, and cerebral edema occurs, resulting in ischemia and encephalopathy. With increasing blood pressure, cerebral autoregulation is impaired resulting in cerebral regions of ischemia as well as microhemorrhage, each of which may initiate a seizure focus. […] Factors associated with endothelial dysfunction have been shown to be increased in the systemic circulation of women suffering from eclampsia. These include the following: Cellular fibronectin, Von Willebrand factor, Cell adhesion molecules (ie, P-selectin, vascular endothelial adhesion molecule-1 [VCAM-1]), Intercellular adhesion molecule-1 [ICAM-1]), Cytokines (ie, interleukin-6 [IL-6]), Tumor necrosis factor- [TNF-].

• #50 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #51

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  CO, a metabolite produced by HO, is known to have vasodilatory properties on placental vasculature, reducing placental perfusion pressure and allowing for increased blood flow. […] Another important factor in preeclampsia is hypoxia-inducible factor 1-alpha (HIF-1), a transcription factor that regulates cell responses to hypoxic environments, such as the ischemic placenta. […] Furthermore, they found that downregulation of HIF-1 in these preeclampsia rat models resulted in a significant reduction in hypertension and proteinuria compared to control rats, thus directly implicating elevated HIF-1 in the pathogenesis of preeclampsia. […] The renin-angiotensin system (RAS) also likely plays a role in preeclampsia. […] This relationship has a dose dependent relationship with levels of AT1-AA positively correlating with the severity of disease.

• #52 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #53 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  Oxidative stress is required for the development of hypoxic injury and has been investigated as a key factor in the pathogenesis of preeclampsia. […] In preeclampsia, hypoxia at the implantation site can contribute to lesion formation, leading to poor placentation. […] Increased levels of HIF-1 can induce secretion of soluble vascular endothelial growth factor receptor-1 (sFlt-1), which is known to be a major factor influencing the pathogenesis of preeclampsia. […] The pathophysiology is partly explained as poor placentation, which is caused by impaired trophoblast invasion. […] Recently, the two-stage disorder theory was proposed to explain the pathogenesis of preeclampsia. […] Shallow placentation results in unsuccessful vascular transformation, impairing fetal viability and increasing the risk for preeclampsia.

• #54

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  CO, a metabolite produced by HO, is known to have vasodilatory properties on placental vasculature, reducing placental perfusion pressure and allowing for increased blood flow. […] Another important factor in preeclampsia is hypoxia-inducible factor 1-alpha (HIF-1), a transcription factor that regulates cell responses to hypoxic environments, such as the ischemic placenta. […] Furthermore, they found that downregulation of HIF-1 in these preeclampsia rat models resulted in a significant reduction in hypertension and proteinuria compared to control rats, thus directly implicating elevated HIF-1 in the pathogenesis of preeclampsia. […] The renin-angiotensin system (RAS) also likely plays a role in preeclampsia. […] This relationship has a dose dependent relationship with levels of AT1-AA positively correlating with the severity of disease.

• #55 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #56 Hypoxia in the pathogenesis of preeclampsia

  https://www.jstage.jst.go.jp/article/jsshp/5/2/5_HRP2017-014/_html/-char/en

  HIF-1 is expressed at high levels in the preeclamptic placenta and induces the production of sFlt-1 and sEng. […] HIF is thus critical for the pathogenesis of preeclampsia. […] Inflammation is integral to the pathogenesis of preeclampsia. […] Severe placental hypoxia could induce the expression and activity of EPO in preeclampsia. […] Preeclampsia involves disturbance of the EPC mobilization from bone marrow into maternal circulation. […] HIF-1 is thought to affect the pathogenesis of preeclampsia through several distinct mechanisms. […] Decreased levels of 2-methoxyestradiol (2-ME) result in elevated levels of sFlt-1. […] Under hypoxic conditions, the balance between HIF-1 and HIF-2 is important for the process of inflammation in the pathogenesis of preeclampsia. […] PGAM appears to be another important factor mediating the pathogenesis of preeclampsia; however, the underlying mechanism remains to be elucidated. […] In the pathogenesis of preeclampsia, the process of placentation early in pregnancy under hypoxic conditions is critical. […] Under hypoxic conditions, the HIF-PGAM axis is thought to play an important role in the pathogenesis of preeclampsia.

• #57 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. […] Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. […] It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. […] One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. […] In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. […] Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p.

• #58 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  During normal placental development, extravillous cytotrophoblast invades the decidual and myometrial spiral arteries. These spiral arteries then lose their endothelial nature and transform themselves from high resistance vessels into large vessels capable of providing adequate placental perfusion to supply nourishment to the developing fetus. This results in impaired spiral artery remodeling and relative placental ischemia. A trophoblast defect can cause shallow placentation, placental ischemia, insufficient spiral artery transformation and the maternal syndrome of preeclampsia. […] The NK cells produce angiogenesis-promoting cytokines and proteins but cannot remodel spiral arteries downstream. Furthermore, PE has been shown to activate circulating T and NK cells. […] Hypoxia-inducible factors (HIF) 1 and 2, markers of cellular oxygen deficiency, were detected in high quantities in the placentas of PE patients.

• #59 European Journal of Translational and Clinical Medicine

  https://ejtcm.gumed.edu.pl/articles/156837

  During normal placental development, extravillous cytotrophoblast invades the decidual and myometrial spiral arteries. These spiral arteries then lose their endothelial nature and transform themselves from high resistance vessels into large vessels capable of providing adequate placental perfusion to supply nourishment to the developing fetus. This results in impaired spiral artery remodeling and relative placental ischemia. A trophoblast defect can cause shallow placentation, placental ischemia, insufficient spiral artery transformation and the maternal syndrome of preeclampsia. […] The NK cells produce angiogenesis-promoting cytokines and proteins but cannot remodel spiral arteries downstream. Furthermore, PE has been shown to activate circulating T and NK cells. […] Hypoxia-inducible factors (HIF) 1 and 2, markers of cellular oxygen deficiency, were detected in high quantities in the placentas of PE patients.

• #60 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Matrix metalloproteinases (MMPs) are of great importance in the formation of endothelial dysfunction in PE. […] Evidence on the involvement of the renin-angiotensin-aldosterone system in PE pathogenesis has been obtained. […] Immune maladjustment of the mothers body also contributes to PE development. […] One of the components of the pathogenesis of PE is the deregulation of the complement system, which is most often associated with the presence of mutations in genes that control the biosynthesis of complement activation regulators. […] The main component of the arterial hypertension pathophysiology in PE is the biologically imbalanced active substances produced by endothelial cells, which are involved in vascular tone regulation. […] To date, a large number of studies have been conducted that comprise the information about 130 possible PE risk factors, covering a large list of comorbidities, biomarkers, environmental factors, and genetic determinants.

• #61 Pre-eclampsia: its pathogenesis and pathophysiolgy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4928171/

  The exact mechanism for this is not known but various factors, such as abnormal genetic variations, biology of the trophoblasts or defective trophoblast differentiation acting together with extrinsic factors, such as maternal constitutional factors, action of macrophage defense mechanisms, impaired action of dNK cells and maternal endothelial cells have been advanced. […] It is therefore believed that placental ischaemiareperfusion injury is central to the development of PE. […] There is increasing evidence that suggests an imbalance between pro-angiogenic and anti-angiogenic factors are responsible for the pathophysiological effects seen in PE, and these appear before clinical signs are apparent. […] The disproportionate levels of anti-angiogenic factors such as sEng and sFlt-1, and pro-angiogenic factors such as VEGF, PlGF and TGF, are believed to cause generalised maternal endothelial dysfunctions, leading to hypertension, renal endotheliosis and blood coagulation.

• #62 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. […] Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. […] It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. […] One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. […] In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. […] Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p.

• #63 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Oxidative damage to the placenta induces apoptosis processes, such as the release of various antiangiogenic factors, proinflammatory cytokines, and vasoactive compounds into the mothers bloodstream, which develops major systemic endothelial cell dysfunction, accompanied by inflammation and vasoconstriction. […] Endothelial dysfunction is central to the maternal syndrome pathogenesis of PE and underlies the imbalance of vasoactive mediators, which induces a shift toward increased vasoconstrictor production. […] An endogenous antiangiogenic factor (endostatin), sFlt1, is a potent VEGF antagonist that is significantly elevated in PE. […] Increased expression of sFlt1 (in vitro) induces glomerular endotheliosis with the disappearance of fenestras, which histologically resembles renal damage in PE.

• #64 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Preeclampsia is a serious complication of pregnancy where it affects 5–8% of all pregnancies. […] Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. […] The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. […] At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. […] Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. […] Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension.

• #65 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Preeclampsia is a serious complication of pregnancy where it affects 5–8% of all pregnancies. […] Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. […] The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. […] At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. […] Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. […] Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension.

• #66 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Preeclampsia is a serious complication of pregnancy where it affects 5–8% of all pregnancies. […] Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. […] The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. […] At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. […] Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. […] Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension.

• #67 Eclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/253960-overview

  Many uterovascular changes occur when a woman is pregnant. It is believed that these changes are due to the interaction between fetal and maternal allografts and result in systemic and local vascular changes. It has been shown that in patients with eclampsia, the development of uteroplacental arteries is hindered. […] It is believed that in eclampsia there is abnormal cerebral blood flow in the setting of extreme hypertension. The regulation of cerebral perfusion is inhibited, vessels become dilated with increased permeability, and cerebral edema occurs, resulting in ischemia and encephalopathy. With increasing blood pressure, cerebral autoregulation is impaired resulting in cerebral regions of ischemia as well as microhemorrhage, each of which may initiate a seizure focus. […] Factors associated with endothelial dysfunction have been shown to be increased in the systemic circulation of women suffering from eclampsia. These include the following: Cellular fibronectin, Von Willebrand factor, Cell adhesion molecules (ie, P-selectin, vascular endothelial adhesion molecule-1 [VCAM-1]), Intercellular adhesion molecule-1 [ICAM-1]), Cytokines (ie, interleukin-6 [IL-6]), Tumor necrosis factor- [TNF-].

• #68 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Preeclampsia is a serious complication of pregnancy where it affects 5–8% of all pregnancies. […] Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. […] The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. […] At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. […] Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. […] Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension.

• #69 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  It is widely accepted that abrupt remodeling of the uterine spiral arteries plays a key role in the pathogenesis of early onset preeclampsia. […] However, there is increasing evidence that damage to the podocytes, the visceral epithelial glomerular cell, is largely responsible for the proteinuria. […] In this context podocyturia (loss of podocytes in the urine), along shedding of slit diaphragm proteins such as nephrin, podocin, synaptopodin and podocalyxin were noticed in preeclampsia, and even precede the typical clinical features of preeclampsia by several weeks. […] The end result of this disruption of the glomerular filtration barrier and podocyte detachment is proteinuria. […] One of the main mediators of the adverse renal consequences of preeclampsia is ET-1. […] However, in the last decade, there is growing evidence that imbalance between the proangiogenic and anti angiogenic factors plays a key role in podocyte injury.

• #70 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  It is widely accepted that abrupt remodeling of the uterine spiral arteries plays a key role in the pathogenesis of early onset preeclampsia. […] However, there is increasing evidence that damage to the podocytes, the visceral epithelial glomerular cell, is largely responsible for the proteinuria. […] In this context podocyturia (loss of podocytes in the urine), along shedding of slit diaphragm proteins such as nephrin, podocin, synaptopodin and podocalyxin were noticed in preeclampsia, and even precede the typical clinical features of preeclampsia by several weeks. […] The end result of this disruption of the glomerular filtration barrier and podocyte detachment is proteinuria. […] One of the main mediators of the adverse renal consequences of preeclampsia is ET-1. […] However, in the last decade, there is growing evidence that imbalance between the proangiogenic and anti angiogenic factors plays a key role in podocyte injury.

• #71 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  It is widely accepted that abrupt remodeling of the uterine spiral arteries plays a key role in the pathogenesis of early onset preeclampsia. […] However, there is increasing evidence that damage to the podocytes, the visceral epithelial glomerular cell, is largely responsible for the proteinuria. […] In this context podocyturia (loss of podocytes in the urine), along shedding of slit diaphragm proteins such as nephrin, podocin, synaptopodin and podocalyxin were noticed in preeclampsia, and even precede the typical clinical features of preeclampsia by several weeks. […] The end result of this disruption of the glomerular filtration barrier and podocyte detachment is proteinuria. […] One of the main mediators of the adverse renal consequences of preeclampsia is ET-1. […] However, in the last decade, there is growing evidence that imbalance between the proangiogenic and anti angiogenic factors plays a key role in podocyte injury.

• #72 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  It is widely accepted that abrupt remodeling of the uterine spiral arteries plays a key role in the pathogenesis of early onset preeclampsia. […] However, there is increasing evidence that damage to the podocytes, the visceral epithelial glomerular cell, is largely responsible for the proteinuria. […] In this context podocyturia (loss of podocytes in the urine), along shedding of slit diaphragm proteins such as nephrin, podocin, synaptopodin and podocalyxin were noticed in preeclampsia, and even precede the typical clinical features of preeclampsia by several weeks. […] The end result of this disruption of the glomerular filtration barrier and podocyte detachment is proteinuria. […] One of the main mediators of the adverse renal consequences of preeclampsia is ET-1. […] However, in the last decade, there is growing evidence that imbalance between the proangiogenic and anti angiogenic factors plays a key role in podocyte injury.

• #73 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Excessive production of antiangiogenic sFlt-1 and sEng reduces the bioavailability of free pro-angiogenic PlGF and VEGF, by binding and neutralizes VEGF and PlGF, thus reducing the availability of free VEGF for fetal and placental angiogenesis. […] In comparison, the sEng is implicated in neutralizing TGF- β, an anti-inflammatory growth factor that activates eNOS. […] This imbalance leads to systemic endothelial dysfunction, including in the kidney, where disruption of slit diaphragm was reported, as VEGF is essential for the maintenance glomerular barrier. […] Support for the adverse effect of preeclampsia on glomerular barrier was reported by Henao et al. […] These authors demonstrated that when a human podocyte cell line was stimulated with serum from women with preeclampsia, disruption of CD2AP, podocin and actin were observed, but not when sera from normal pregnancy was added.

• #74 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  Excessive production of antiangiogenic sFlt-1 and sEng reduces the bioavailability of free pro-angiogenic PlGF and VEGF, by binding and neutralizes VEGF and PlGF, thus reducing the availability of free VEGF for fetal and placental angiogenesis. […] In comparison, the sEng is implicated in neutralizing TGF- β, an anti-inflammatory growth factor that activates eNOS. […] This imbalance leads to systemic endothelial dysfunction, including in the kidney, where disruption of slit diaphragm was reported, as VEGF is essential for the maintenance glomerular barrier. […] Support for the adverse effect of preeclampsia on glomerular barrier was reported by Henao et al. […] These authors demonstrated that when a human podocyte cell line was stimulated with serum from women with preeclampsia, disruption of CD2AP, podocin and actin were observed, but not when sera from normal pregnancy was added.

• #75

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  CO, a metabolite produced by HO, is known to have vasodilatory properties on placental vasculature, reducing placental perfusion pressure and allowing for increased blood flow. […] Another important factor in preeclampsia is hypoxia-inducible factor 1-alpha (HIF-1), a transcription factor that regulates cell responses to hypoxic environments, such as the ischemic placenta. […] Furthermore, they found that downregulation of HIF-1 in these preeclampsia rat models resulted in a significant reduction in hypertension and proteinuria compared to control rats, thus directly implicating elevated HIF-1 in the pathogenesis of preeclampsia. […] The renin-angiotensin system (RAS) also likely plays a role in preeclampsia. […] This relationship has a dose dependent relationship with levels of AT1-AA positively correlating with the severity of disease.

• #76 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Matrix metalloproteinases (MMPs) are of great importance in the formation of endothelial dysfunction in PE. […] Evidence on the involvement of the renin-angiotensin-aldosterone system in PE pathogenesis has been obtained. […] Immune maladjustment of the mothers body also contributes to PE development. […] One of the components of the pathogenesis of PE is the deregulation of the complement system, which is most often associated with the presence of mutations in genes that control the biosynthesis of complement activation regulators. […] The main component of the arterial hypertension pathophysiology in PE is the biologically imbalanced active substances produced by endothelial cells, which are involved in vascular tone regulation. […] To date, a large number of studies have been conducted that comprise the information about 130 possible PE risk factors, covering a large list of comorbidities, biomarkers, environmental factors, and genetic determinants.

• #77

  https://www.openaccessjournals.com/articles/pathophysiologyof-hypertension-inpreeclampsia.html

  CO, a metabolite produced by HO, is known to have vasodilatory properties on placental vasculature, reducing placental perfusion pressure and allowing for increased blood flow. […] Another important factor in preeclampsia is hypoxia-inducible factor 1-alpha (HIF-1), a transcription factor that regulates cell responses to hypoxic environments, such as the ischemic placenta. […] Furthermore, they found that downregulation of HIF-1 in these preeclampsia rat models resulted in a significant reduction in hypertension and proteinuria compared to control rats, thus directly implicating elevated HIF-1 in the pathogenesis of preeclampsia. […] The renin-angiotensin system (RAS) also likely plays a role in preeclampsia. […] This relationship has a dose dependent relationship with levels of AT1-AA positively correlating with the severity of disease.

• #78 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Matrix metalloproteinases (MMPs) are of great importance in the formation of endothelial dysfunction in PE. […] Evidence on the involvement of the renin-angiotensin-aldosterone system in PE pathogenesis has been obtained. […] Immune maladjustment of the mothers body also contributes to PE development. […] One of the components of the pathogenesis of PE is the deregulation of the complement system, which is most often associated with the presence of mutations in genes that control the biosynthesis of complement activation regulators. […] The main component of the arterial hypertension pathophysiology in PE is the biologically imbalanced active substances produced by endothelial cells, which are involved in vascular tone regulation. […] To date, a large number of studies have been conducted that comprise the information about 130 possible PE risk factors, covering a large list of comorbidities, biomarkers, environmental factors, and genetic determinants.

• #79 Cause Of Preeclampsia

  https://www.preeclampsia.org/cause-of-preeclampsia

  If the ability of these antiangiogenic proteins to cause preeclampsia is confirmed by research in humans, why the placenta overproduces them remains unknown. […] Preeclampsia may have multiple causes, and other leads are being investigated, including prostaglandins, digoxin-like molecules, immunological mechanisms, autoantibodies that trigger receptors that lead to vessel constriction (agonistic autoantibodies to the angiotensin-1 receptor), oxidative stress, mitochondrial pathology, the impact of hypertension and prehypertension on endovascular health, and genes sensitive to low-oxygen environments. […] While we are moving closer to historically elusive answers, the true cause of preeclampsia remains unknown. Successful ongoing research needs far more support and funding.

• #80 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  The interplay between glycosylation and galectins significantly impacts the behavior of trophoblasts and immune cells at the maternal–fetal interface. Abnormal glycosylation disrupts galectin-mediated signaling pathways, leading to endothelial dysfunction and increased inflammation, as seen in PE. Enhanced expression of specific glycosyltransferases in the placenta modifies glycan structures, affecting galectin binding and function, thus contributing to PE’s pathophysiology. […] The role of ferroptosis, a form of iron-dependent cell death, has also been implicated in the pathogenesis of PE. Ferroptosis is driven by the accumulation of lipid peroxides and is regulated by the activity of glutathione peroxidase 4 (GPX4) and the availability of iron. In PE, dysregulation of iron metabolism and increased lipid peroxidation contribute to ferroptosis in placental trophoblasts, leading to placental dysfunction and exacerbating oxidative stress.

• #81 Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening | BMC Pregnancy and Childbirth | Full Text

  https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-023-06211-2

  Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. […] Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs. […] The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. […] PKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. […] A total of 54 autophagy-related genes were filtered by WGCNA.

• #82 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  The interplay between glycosylation and galectins significantly impacts the behavior of trophoblasts and immune cells at the maternal–fetal interface. Abnormal glycosylation disrupts galectin-mediated signaling pathways, leading to endothelial dysfunction and increased inflammation, as seen in PE. Enhanced expression of specific glycosyltransferases in the placenta modifies glycan structures, affecting galectin binding and function, thus contributing to PE’s pathophysiology. […] The role of ferroptosis, a form of iron-dependent cell death, has also been implicated in the pathogenesis of PE. Ferroptosis is driven by the accumulation of lipid peroxides and is regulated by the activity of glutathione peroxidase 4 (GPX4) and the availability of iron. In PE, dysregulation of iron metabolism and increased lipid peroxidation contribute to ferroptosis in placental trophoblasts, leading to placental dysfunction and exacerbating oxidative stress.

• #83 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  The interplay between glycosylation and galectins significantly impacts the behavior of trophoblasts and immune cells at the maternal–fetal interface. Abnormal glycosylation disrupts galectin-mediated signaling pathways, leading to endothelial dysfunction and increased inflammation, as seen in PE. Enhanced expression of specific glycosyltransferases in the placenta modifies glycan structures, affecting galectin binding and function, thus contributing to PE’s pathophysiology. […] The role of ferroptosis, a form of iron-dependent cell death, has also been implicated in the pathogenesis of PE. Ferroptosis is driven by the accumulation of lipid peroxides and is regulated by the activity of glutathione peroxidase 4 (GPX4) and the availability of iron. In PE, dysregulation of iron metabolism and increased lipid peroxidation contribute to ferroptosis in placental trophoblasts, leading to placental dysfunction and exacerbating oxidative stress.

• #84 Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening | BMC Pregnancy and Childbirth | Full Text

  https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-023-06211-2

  In this study, we applied a WGCNA analysis based on public databases and performed GO and KEGG enrichment analysis for the most correlated module. […] It turned out that hypoxia and oxidative stress were the major bioprocesses in PE, which is consistent with our prior knowledge. […] After further screening via the String database, we found 3 autophagy-related hub genes overexpressed in the PE group, namely, PKM, LEP, and HK2. […] These results indicated that autophagy might mediate PE via metabolism disorder. […] The interacting relations between leptin and autophagy varies in a tissue-specific pattern. […] Therefore, we further investigated the regulation network among hub genes, lncRNA and miRNA to explore the underlying mechanisms of hub genes in the pathogenesis of PE and found that the signaling pathway involved were mainly autophagy and other metabolic pathways. […] In summary, this research has identified PKM, LEP, and HK2 to be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via targeting autophagy, metabolism and immune microenvironment.

• #85 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  The angiogenic imbalance hypothesis highlights the disruption of balance between pro-angiogenic factors (vascular endothelial growth factor (VEGF), placental growth factor (PlGF)), and anti-angiogenic factors (sFlt-1, sEng), impairing blood vessel formation and function, which results in endothelial dysfunction and reduced placental perfusion. […] The placental hypoxia and oxidative stress hypothesis suggests that oxidative stress due to placental hypoxia contributes to PE. Placental hypoxia increases the production of reactive oxygen species (ROS), which damage placental and maternal endothelial cells, impairing their function. […] The metabolic syndrome hypothesis links preeclampsia to metabolic syndrome and associated conditions, including obesity, insulin resistance, and hypertension. Metabolic disturbances lead to systemic inflammation and endothelial dysfunction, contributing to PE development.

• #86 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. […] Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. […] It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. […] One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. […] In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. […] Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p.

• #87 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. […] Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. […] It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. […] One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. […] In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. […] Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p.

• #88 Developmentally Delayed Epigenetic Reprogramming Underlying the Pathogenesis of Preeclampsia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.05.08.085290v3

  Preeclampsia, a life-threatening pregnancy complication characterized by hypertension and multiorgan damage, affects 2-5% of pregnancies and causes 76,000 deaths per year. […] Most preeclampsia associated syndromes immediately dispel after removal of placenta, indicating a casual role of placenta in the pathogenesis. […] Failed transformation of spiral artery due to insufficient invasion and excessive apoptosis of trophoblast suggested developmental defects in preeclampsia placenta. […] However, the underlying molecular mechanisms that affected placenta development in preeclampsia remained elusive. […] Here we show that, in preeclampsia placenta, the epigenetic landscape formed during extraembryonic tissue differentiation was disrupted: dramatic chromatin accessibility shift affected known and novel genes implicated in preeclampsia.

• #89 Developmentally Delayed Epigenetic Reprogramming Underlying the Pathogenesis of Preeclampsia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.05.08.085290v3

  Preeclampsia, a life-threatening pregnancy complication characterized by hypertension and multiorgan damage, affects 2-5% of pregnancies and causes 76,000 deaths per year. […] Most preeclampsia associated syndromes immediately dispel after removal of placenta, indicating a casual role of placenta in the pathogenesis. […] Failed transformation of spiral artery due to insufficient invasion and excessive apoptosis of trophoblast suggested developmental defects in preeclampsia placenta. […] However, the underlying molecular mechanisms that affected placenta development in preeclampsia remained elusive. […] Here we show that, in preeclampsia placenta, the epigenetic landscape formed during extraembryonic tissue differentiation was disrupted: dramatic chromatin accessibility shift affected known and novel genes implicated in preeclampsia.

• #90 Developmentally Delayed Epigenetic Reprogramming Underlying the Pathogenesis of Preeclampsia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.05.08.085290v3

  DNA methylation defects in preeclampsia affected lineage-defining PcG-controlled loci in trophectoderm. […] LTR12 retrotransposons associated with VCT/SCT-specific genes were hypermethylated. […] Meanwhile, hundreds of PcG-regulated EVT-specific gene promoters, which otherwise undergone post-ZGA extraembryonic-tissue-specific de novo methylation, were hypomethylated and hyper-activated. […] Together, these epigenetic defects resulted in placenta developmental delay in preeclampsia. […] The defective methylation pattern could be detected in serum cfDNA, and could be used to accurately predict preeclampsia at early pregnancy weeks in independent validation cohorts. […] Our data suggests that the preeclampsia placenta represents a stalled state of epigenetic reprogramming en route of development from trophectoderm to normal placenta.

• #91 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Generally, the mechanisms of early and late PE occurrence are different. […] Thus, late PE development, which was registered in 88% of all cases, is mainly due to maternal causes (metabolic syndrome, arterial hypertension, chronic kidney disease, etc.) in combination with placental dysfunction. […] A trigger factor for early PE is a placentation impairment at the initial gestational stages. […] With PE, these processes are disrupted, which ultimately leads to defective trophoblast invasion and impaired formation of uteroplacental blood flow. […] Low oxygen levels stimulate increased expression of hypoxia-induced factors (HIF-1 and HIF-2) and transforming growth factor (TGF-), which also inhibits the transition of the trophoblast to the invasive type. […] One of the mechanisms that disrupt the invasion processes is the persistent hypoxia-mediated overexpression of HIF-1/HIF-2 and TGF-.

• #92 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #93 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #94 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #95 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Generally, the mechanisms of early and late PE occurrence are different. […] Thus, late PE development, which was registered in 88% of all cases, is mainly due to maternal causes (metabolic syndrome, arterial hypertension, chronic kidney disease, etc.) in combination with placental dysfunction. […] A trigger factor for early PE is a placentation impairment at the initial gestational stages. […] With PE, these processes are disrupted, which ultimately leads to defective trophoblast invasion and impaired formation of uteroplacental blood flow. […] Low oxygen levels stimulate increased expression of hypoxia-induced factors (HIF-1 and HIF-2) and transforming growth factor (TGF-), which also inhibits the transition of the trophoblast to the invasive type. […] One of the mechanisms that disrupt the invasion processes is the persistent hypoxia-mediated overexpression of HIF-1/HIF-2 and TGF-.

• #96 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  The situation was even grimmer in women who experienced preeclampsia by 34 weeks of gestation. […] The high mortality rate could be explained by the findings that early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, CNS, renal, hepatic, and other morbidity and was evident by end target damage. […] Collectively, these findings suggest that the risk of morbidity/mortality among preeclamptic women is related to the severity the disease and gestational age at onset, namely early (<34 weeks) or late (>34 weeks). […] However, it should be emphasized that if the mother has a genetic predisposition to cardiovascular disease, then it is this rather than pre-eclampsia per se that causes the increased morbidity in later life as outlined above. […] It is now appreciated that early- and late-onset pre-eclampsia have different pathophysiologies, thus advancing our understanding of the syndrome.

• #97 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #98 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #99 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  In early-onset, also referred to as placental pre-eclampsia, there is clear evidence of reduced maternal spiral artery conversion in early pregnancy. […] This is associated with placental malperfusion, and gross and molecular pathology of the placental tissues. […] Oxidative stress of the placenta causes increased secretion of sFLT-1 and reduced PlGF, reflecting the biomarker patterns. […] In late-onset pre-eclampsia, called also maternal preeclampsia, there is little evidence of reduced arterial conversion and placental perfusion is maintained or even increased. […] Thus, there is only minimal placental stress so that sFLT and placental growth factor (PlGF) secretion by the placenta are close to the normal range. […] These cases, which represent nearly 80% of pre-eclampsia, are now thought to be due to a genetic maternal pre-disposition to cardiovascular disease, which manifests as pre-eclampsia during the stress-test of pregnancy.

• #100 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Generally, the mechanisms of early and late PE occurrence are different. […] Thus, late PE development, which was registered in 88% of all cases, is mainly due to maternal causes (metabolic syndrome, arterial hypertension, chronic kidney disease, etc.) in combination with placental dysfunction. […] A trigger factor for early PE is a placentation impairment at the initial gestational stages. […] With PE, these processes are disrupted, which ultimately leads to defective trophoblast invasion and impaired formation of uteroplacental blood flow. […] Low oxygen levels stimulate increased expression of hypoxia-induced factors (HIF-1 and HIF-2) and transforming growth factor (TGF-), which also inhibits the transition of the trophoblast to the invasive type. […] One of the mechanisms that disrupt the invasion processes is the persistent hypoxia-mediated overexpression of HIF-1/HIF-2 and TGF-.

• #101 Frontiers | Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00973/full

  The situation was even grimmer in women who experienced preeclampsia by 34 weeks of gestation. […] The high mortality rate could be explained by the findings that early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, CNS, renal, hepatic, and other morbidity and was evident by end target damage. […] Collectively, these findings suggest that the risk of morbidity/mortality among preeclamptic women is related to the severity the disease and gestational age at onset, namely early (<34 weeks) or late (>34 weeks). […] However, it should be emphasized that if the mother has a genetic predisposition to cardiovascular disease, then it is this rather than pre-eclampsia per se that causes the increased morbidity in later life as outlined above. […] It is now appreciated that early- and late-onset pre-eclampsia have different pathophysiologies, thus advancing our understanding of the syndrome.

• #102 Pre-eclampsia: pathogenesis, novel diagnostics and therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6472952/

  Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-eclampsia. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. […] The past two decades have seen major advances in the field of pre-eclampsia, although the underlying pathogenesis remains elusive. Currently, the disease can be understood in terms of both placental and maternal dysfunction. Various genetic, angiogenic, structural and metabolic pathways have been implicated in pre-eclampsia, including spiral artery remodelling, placental oxygenation, redox and immune tolerance at the maternalfetal interface and the balance of angiogenic and antiangiogenic factors. In particular, certain antiangiogenic proteins have emerged as key pathogenic mediators of the maternal disease, and their discovery has provided opportunities for the development of novel diagnostics such as risk calculators, prediction models and triage tools.

• #103 Preeclampsia: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-pathogenesis/print

  Preeclampsia is a pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria or hypertension and end-organ dysfunction with or without proteinuria after 20 weeks of gestation. […] The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which leads to the progressive release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause hypertension, vasospasm, platelet aggregation, and the other manifestations of the disease. […] However, the trigger for abnormal placental development and the subsequent cascade of events remains unknown. […] Our current understanding of mechanisms causing the pathologic changes observed in preeclampsia will be reviewed here.

• #104 A Narrative Review on the Pathophysiology of Preeclampsia

  https://www.mdpi.com/1422-0067/25/14/7569

  Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia’s effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

• #105 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046/en_US

  Preeclampsia is a serious complication of pregnancy and complicates its course in 2-8% of all cases. […] Of particular interest is the study of the molecular mechanisms of etiopathogenesis and risk factors for preeclampsia, which, unfortunately, are currently poorly studied and understood, thus dictating the need for further study of this complication of pregnancy. […] This article discusses the current understanding of the etiology, pathogenesis and risk factors for preeclampsia. […] The mechanisms of PE occurrence are extensively studied worldwide, and 30 hypotheses for the development of this pregnancy complication were reported, most of which placentation disorders are the most significant. […] The two-stage model of PE development that was introduced by Redman in 1991 is currently generally accepted. At stage 1 of PE, abnormal placentation occurs in early pregnancy, which leads to disseminated endothelial dysfunction and maternal syndrome at stage 2.

• #106 An Update Review of the Pathogenesis Hypothesis in Preeclampsia

  https://www.imrpress.com/journal/CEOG/49/8/10.31083/j.ceog4908170/htm

  At present, the pathogenesis of preeclampsia is still unclear, we wrote this article to make a uptodate review of this disease. […] At present, the pathogenesis of preeclampsia is still unclear, large number of hypothesis have been proposed for the placental dysfunction, including oxidative stress, abnormal natural killer cells at the maternal-fetal interface, and genetic and environmental factors, though none have conclusive evidence in humans. […] The pathogenesis of preeclampsia is still unclear, the theory of Genetic, Inflammatory Response, Immune Imbalance in Maternal-Fetal Interface, Oxidative Stress, Vascular Endothelial Cell Damage are supposed involved in the progress of preeclampsia. […] Although there are various theories mentioned above, none of them can fully explain all the biological behaviors of preeclampsia. More research is needed on the mechanism of preeclampsia.

• #107 Research trajectory of the mechanism of preeclampsia: a scientometric perspective | Journal of Health, Population and Nutrition | Full Text

  https://jhpn.biomedcentral.com/articles/10.1186/s41043-025-00806-5

  This study aims to conduct a scientometric analysis on the research history and emerging trends of the pathogenesis of preeclampsia using CiteSpace and VOSviewer software. […] The pathogenesis of preeclampsia remains unclear, but the widely accepted 'two-stage theory’ suggests that the disorder involves inadequate trophoblast cell growth, invasion, and movement in the first stage, leading to abnormal placental positioning and inadequate remodeling of spiral arteries. This results in ongoing placental issues such as ischemia and hypoxia. The second stage involves the release of various substances by the placenta into the bloodstream, which affects blood vessels and triggers an excessive inflammatory response throughout the body. […] Current research on the mechanism of preeclampsia primarily focuses on placental ischemia and hypoxia, inflammatory response and immune disorders, angiogenic factor imbalance, abnormal epigenetic modifications, and intestinal flora imbalance.

• #108 Pre-eclampsia | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-023-00417-6

  Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. […] Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. […] Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. […] Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

• #109

  https://journals.lww.com/cjasn/fulltext/2016/06000/preeclampsia__updates_in_pathogenesis,.22.aspx

  Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. […] In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. […] The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. […] We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

Zobacz więcej