Materiały źródłowe

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9405799/

  Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9405799/

  Atherosclerosis is the main cause of cardiovascular-related death worldwide. It is a thickening and hardening of the arterial wall, accompanies aging, and is related to major adverse impact on the cardiovascular system and various other diseases. Elevated plasma cholesterol level (150 mg/dL) is a major cause of the development of atherosclerosis. […] CAD is caused primarily by plaque formation within the intima of the vessel wall, with plaque being defined as a fatty material growing inside intima along with a severe inflammation, especially if the inflammation is chronic. This in turn causes difficulties in supplying the cardiomyocytes with enough blood, oxygen, and nutrients. […] Endothelial dysfunction in modern cardiovascular medicine is described as changes in the production and availability of endothelial-derived NO, prostacyclin, and endothelin, as well as their impact on vascular reactivity. In this case, reactive oxygen species (ROS) such as H2O2 reach the regulatory molecules, which leads to the activation of the cells.

• #1 Cardiovascular Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535419/

  The cardiovascular system consists of the heart and its blood vessels. A wide array of problems can arise within the cardiovascular system, a few of which include endocarditis, rheumatic heart disease, and conduction system abnormalities. Cardiovascular disease, also known as heart disease, refers to the following 4 entities: coronary artery disease (CAD) which is also referred to as coronary heart disease (CHD), cerebrovascular disease, peripheral artery disease (PAD), and aortic atherosclerosis. CAD results from decreased myocardial perfusion that causes angina due to ischemia and can result in myocardial infarction (MI), and/or heart failure. It accounts for one-third to one-half of all cases of cardiovascular disease. […] Atherosclerosis is the pathogenic process in the arteries and the aorta that can potentially cause disease as a consequence of decreased or absent blood flow from stenosis of the blood vessels. It involves multiple factors dyslipidemia, immunologic phenomena, inflammation, and endothelial dysfunction. These factors are believed to trigger the formation of fatty streak, which is the hallmark in the development of the atherosclerotic plaque; a progressive process that may occur as early as in the childhood. This process comprises intimal thickening with subsequent accumulation of lipid-laden macrophages (foam cells) and extracellular matrix, followed by aggregation and proliferation of smooth muscle cells constituting the formation of the atheroma plaque. As this lesions continue to expand, apoptosis of the deep layers can occur, precipitating further macrophage recruitment that can become calcified and transition to atherosclerotic plaques. […] Measures aimed to prevent the progression of atherosclerosis are the hallmark for primary prevention of CVD. Risk factor and lifestyle modification are paramount in the prevention of CVD.

• #1 Arteriosclerosis / atherosclerosis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569

  Atherosclerosis is the buildup of fats, cholesterol and other substances in and on the artery walls. This buildup is called plaque. The plaque can cause arteries to narrow, blocking blood flow. The plaque also can burst, leading to a blood clot. […] Once the inner wall of an artery is damaged, blood cells and other substances may collect at the injury site. These substances build up in the inner lining of the artery. […] Over time, fats, cholesterol and other substances also collect on and in the walls of the heart arteries. This buildup is called plaque. Plaque can cause the arteries to narrow. Narrowed arteries can block blood flow. The plaque also can burst, leading to a blood clot. […] If there’s too much cholesterol in the blood, the cholesterol and other substances may form deposits called plaque. Plaque can cause an artery to become narrowed or blocked. If a plaque ruptures, a blood clot can form. Plaque and blood clots can reduce blood flow through an artery.

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9405799/

  The vascular endothelium is the layer of cells lying under the epithelium lining the inside of the vessel and the muscular layer, which is a boundary between the circulating blood and the vascular wall. Its cells are specialized in maintaining vascular homeostasis, which is crucial for the proper functioning of organs, especially the heart. […] The expression of the nicotinamide adenine dinucleotide phosphate oxidase in the vessel wall with the consequent overproduction of NO has been proposed as an initial step in the chronic dysregulation of normal NO production by eNOS, which is characteristic of the monomeric forms of eNOS. […] Taking this into account, the endothelial dysfunction is directly related to a decreased production and sensitivity of cells to NO. As a result, we have an effective disturbance in the functioning of the entire vessel and its homeostasis, which leads to an observation of prothrombotic and proinflammatory phenomena, along with lower susceptibility of the blood vessel wall.

• #1 Pathology of cardiovascular system | PPT

  https://www.slideshare.net/slideshow/pathology-of-cardiovascular-system-192305341/192305341

  The Response to Endothelium Injury Hypothesis 2. Result in endothelial dysfunction that causes endothelial permeability, enhanced leukocyte adhesion alteration in expression of EC gene products (ICAM-1) (VCAM-1) that mediate adhesion of circulating monocytes, lymphocytes and platelets. […] Adhesion of blood monocytes (and other leukocytes) to the endothelium, followed by their migration into the intima and their transformation into macrophages and foam cells. […] Proliferation of SMCs in the intima, and elaboration of extracellular matrix, leading to accumulation of collagen and proteoglycans. Enhanced accumulation of lipids both within cells (macrophages and SMCs) and extracellularly. […] Atherosclerosis causes arterial wall thinning through medial destruction. Cystic medial degeneration of the arterial media Focal loss of elastic and muscle fibers in the aortic media and replacement by cystic spaces filled with myxoid material (hypertension, Marfans syndrome).

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  CAD is caused primarily by plaque formation within the intima of the vessel wall, with plaque being defined as a fatty material growing inside intima along with a severe inflammation, especially if the inflammation is chronic. […] As a result, atherosclerotic plaque may erode or rupture, initially resulting in thrombosis and then a closure of the vessel, leading to myocardial infarction, stroke, limb ischemia, and death. […] Endothelial dysfunction in modern cardiovascular medicine is described as changes in the production and availability of endothelial-derived NO, prostacyclin, and endothelin, as well as their impact on vascular reactivity. […] The endothelial membrane is permeable to compounds such as NO and H2O2, which causes the activation of the transcription factors and protease.

• #1 Immunity, atherosclerosis and cardiovascular disease | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-117

  Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. […] The major direct cause of CVD appears to be rupture of atherosclerotic plaques. […] More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. […] To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. […] The notion of atherosclerosis as an inflammatory disease is based on the finding that immune competent cells are abundant in atherosclerotic lesions, and also are producing cytokines, especially proinflammatory cytokines. […] Even though atherosclerosis per se could decrease blood flow through stenosis and thus induce CVD, the major mechanism appears to be atherothrombosis, usually when plaques are damaged through the effects of proinflammatory cytokines and chemokines on the fibrous cap.

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  Endothelial dysfunction is considered to be the earliest marker of atherosclerosis and, in effect, CAD. […] The expression of the nicotinamide adenine dinucleotide phosphate oxidase in the vessel wall with the consequent overproduction of NO has been proposed as an initial step in the chronic dysregulation of normal NO production by eNOS, which is characteristic of the monomeric forms of eNOS. […] Taking this into account, the endothelial dysfunction is directly related to a decreased production and sensitivity of cells to NO. […] Inflammation in diseases such as polyarteritis nodosa and cryoglobulinemia is driven by IC deposition (antibody-mediated IC formation, microaneurysms). […] The underlying pathogenesis involves many mechanisms such as cell-mediated inflammation, immune complex (IC)-mediated inflammation, and ANCA-mediated inflammation.

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  The vascular endothelium reacts to physical and chemical stimuli through the release of autocrine and paracrine vasoactive agents. […] The NOD-like receptor protein 3 (NLRP3) inflammasome participates in the development of AH. […] Evidence from human and animal studies strongly suggests an association between inflammation and AH. Most recent findings in this field add to the growing body of evidence suggesting that AH is an inflammatory disease, while also drawing attention to the new possibilities for treating AH.

• #1 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9405799/

  The remodeling of the vascular extracellular matrix (ECM) during hypertensive impairment has been associated with the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Several MMPs and TIMPs might participate in the vascular remodeling associated with the AH. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, involved in many physiological and pathological processes, particularly tissue repair and modulation, cellular differentiation, cell mobility, angiogenesis, and cell proliferation, migration, and apoptosis. […] Oxidative stress, resulting in either enhanced ROS production or decreases in antioxidant defense, is associated with an elevated BP, endothelial dysfunction, and vascular remodeling. Oxidative stress and inflammatory responses act cooperatively in the pathogenesis of AH.

• #1 Atherosclerotic cardiovascular disease – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/atherosclerotic-cardiovascular-disease/

  Atherosclerotic cardiovascular disease (ASCVD) is a group of conditions that are caused by atherosclerosis and that can affect different locations throughout the body. […] The pathogenesis of atherosclerosis is precipitated by endothelial damage, which leads to inflammation and the formation of atheromas in vessel walls. […] The pathogenesis of atherosclerosis includes chronic stress on the endothelium, endothelial cell dysfunction, inflammation of the vessel wall, and the accumulation of foam cells that transform into fatty streaks. […] Inflammatory cells in the atheroma secrete matrix metalloproteinases, leading to the weakening of the fibrous cap of the plaque and potential plaque rupture. […] The risk of ASCVD should be estimated using an ASCVD risk calculator to guide timely primary prevention strategies.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  To understand the role of oxidation in the pathology of disease, in particular in those diseases that show abnormalities of diastolic function, it is crucial to elucidate the functional changes that occur during oxidative stress and how they result in HF. […] Classic stimuli of ventricular remodeling such as wall stress, inflammatory cytokines, and neurohormones induce cellular changes that are at least partially mediated via oxidative or nitrosative stress. […] Inflammation plays a central role in the development of HF, particularly in HF with preserved ejection fraction (HFpEF). […] Increased inflammation is an important mechanism contributing to increased risk of HF in diabetic patients. […] The underlying mechanisms of inflammatory-dependent HF in diabetic patients include increased expression levels of interleukins (IL) 1 and 6, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), together with decreased activity of collagen-degrading matrix metalloproteinase.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  By contrast, M2 macrophages exhibit an anti-inflammatory, pro-regenerative phenotype due to their capacity to secrete high levels of anti-inflammatory cytokines, including IL-10 and certain growth factors. […] The pathological processes in many disease models are fueled by macrophage-derived cytokines. […] The mechanisms by which myocardial oxidative stress might impair cardiac function is probably oxidative damage to cellular proteins and membranes, thereby inducing cellular dysfunction or death through apoptosis and/or necrosis. […] ROS may also activate signaling pathways that contribute to ischemic preconditioning, cardioprotection, and myocardial damage, and high levels of ROS induce structural modifications of the sarcomere that impact pump function and the general pathogenesis of HF.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  The heart undergoes extensive structural and functional remodeling in response to injury, central to which is the hypertrophy of cardiac myocytes, which is characterized by the excessive deposition of extracellular matrix. […] Mechanical stress resulting in LV overload can also lead to myocardial inflammation, which manifests as leucocyte infiltration and the myocardial release of pro-inflammatory cytokines. […] Pro-inflammatory cytokines affect LV function, exert a negative inotropic effect, induce abnormalities in cardiac metabolism and energetics, promote myocardial remodeling, and depress myocardial contractility. […] The result is cardiomyocyte hypertrophy, necrosis, and apoptosis, as well as activation of metalloproteinases, impaired expression of their inhibitors, and changes to the extracellular myocardial matrix, which together likely contribute to cardiac remodeling.

• #1 Overview of Coronary Artery Disease – Cardiovascular Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/cardiovascular-disorders/coronary-artery-disease/overview-of-coronary-artery-disease

  The consequences of acute ischemia, collectively referred to as acute coronary syndromes (ACS), depend on the location and degree of obstruction and range from unstable angina, nonST-segment elevation myocardial infarction (NSTEMI), to ST-segment elevation myocardial infarction (STEMI), which can result in transmural infarction, and other complications including malignant ventricular arrhythmias, conduction defects, heart failure, and sudden death. […] Coronary artery spasm is a transient, focal increase in vascular tone, markedly narrowing the lumen and reducing blood flow; symptomatic ischemia (vasospastic angina) may result. […] In arteries with atheroma, the atheroma causes endothelial dysfunction, possibly resulting in local hypercontractility. Proposed mechanisms include loss of sensitivity to intrinsic vasodilators (eg, acetylcholine) and increased production of vasoconstrictors (eg, angiotensin II, endothelin, leukotrienes, serotonin, thromboxane) in the area of the atheroma. […] Coronary artery dissection is a rare, non-traumatic tear in the coronary intima with creation of a false lumen. Blood flowing through the false lumen expands it, which restricts blood flow through the true lumen sometimes causing coronary ischemia or infarction.

• #1 Immunity, atherosclerosis and cardiovascular disease | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-117

  The major risk factors which can be modified for atherosclerosis (and CVD) are hypertension, smoking, diabetes and dyslipidemia. […] OxLDL could play a role both in atherogenesis and in plaque complications. […] The proinflammatory and immune stimulatory effects of oxLDL are mimicked by inflammatory phospholipids, such as lysophosphatidylcholine (LPC), which is a major phospholipid in atherosclerotic lesions. […] The role of cell death as a cause of inflammation in atherosclerosis and plaque rupture is complicated and depends most likely on stage of disease, and naturally, on whether cell death is organized as in apoptosis, or not, as in necrosis. […] Dying cells can activate the innate immune system and induce an inflammatory response with release of the proinflammatory cytokine IL-1beta, activating the inflammasome.

• #1 Association between insulin resistance and the development of cardiovascular disease | Cardiovascular Diabetology | Full Text

  https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0762-4

  For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. […] Insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. […] Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. […] This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. […] Insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium.

• #1 Association between insulin resistance and the development of cardiovascular disease | Cardiovascular Diabetology | Full Text

  https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0762-4

  Several molecular mechanisms contribute to the association between insulin resistance and CVD. […] Insulin resistance causes endothelial cell dysfunction by decreasing the production of nitric oxide from endothelial cells and increasing the release of pro-coagulant factors leading to platelet aggregation. […] In an insulin resistant state, the PI3K pathway is affected whereas the MAP kinase pathway is intact, which causes mitogenic effect of insulin in endothelial cells leading to atherosclerosis. […] Insulin resistance is a key player in the pathogenesis of metabolic diseases like type 2 diabetes and can be observed in several clinical conditions such as breast cancer, rheumatoid arthritis, polycystic ovary syndrome, non-alcoholic fatty liver disease, and CVD. […] The excess of lipids in the cardiomyocyte shunted into non-oxidative pathways results in the accumulation of toxic lipid species (lipotoxicity), which alters cellular signaling and cardiac structure. […] Insulin resistance contributes to generate CVD via two independent pathways: (1) atheroma plaque formation and (2) ventricular hypertrophy and diastolic abnormality.

• #1 Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01055-2

  Epigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses and candidate gene approaches illustrate the multigenic complexity of cardiovascular disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding RNA, which are of importance for cardiovascular disease development and regression. Targeting epigenetic key enzymes, especially the DNA methyltransferases, histone methyltransferases, histone acetylases, histone deacetylases and their regulated target genes, could represent an attractive new route for the diagnosis and treatment of cardiovascular diseases. […] Recent studies have found that epigenetic modification plays an important role in the occurrence and development of cardiovascular diseases. Epigenetics mainly regulates cardiovascular disease-related genes function and expression level through DNA methylation, histone modification, and noncoding RNA regulation, thus affecting cardiovascular disease progression. Epigenetic markers are important molecular markers of cardiovascular disease because they occur early in the disease and involve key cardiovascular pathologically related pathways.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  The role of inflammation in the pathogenesis and progression of HF has important therapeutic and diagnostic implications. […] The significance of inflammation in the development of HFpEF was firmly established in a swine model following induction of the three most common inflammation-associated comorbidities in HFpEF patients: arterial hypertension, diabetes mellitus, and hypercholesterolemia. […] Macrophages are key mediators of the innate immune response, which is involved in the recognition, phagocytosis, and elimination of pathogens. […] Macrophages are classified as either M1 or M2 types. […] M1 macrophages are usually associated with a pro-inflammatory response and are referred to as classically activated macrophages, with induction mediated by IFN, lipopolysaccharide, and TNF-.

• #1 Immunity, atherosclerosis and cardiovascular disease | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-117

  According to the danger hypothesis, endogenous factors (DAMPs) released during cell death induce inflammation. […] HSPs may also activate immune reactions through cross-reactivity with HSP from microorganisms, such as bacteria. […] Infections have been much discussed as potential causes of immune activation and inflammation in atherosclerosis. […] Even though the infectious hypothesis in CVD and atherosclerosis has been studied for some decades, there is still little direct, though rather much circumstantial, evidence of a causative role of infectious agents. […] Inflammation could play a major role to trigger plaque rupture which is the immediate cause of CVD. […] Studies of anti-inflammatory and immune modulatory treatment are underway or discussed. […] Until such treatment studies in humans demonstrate that atherosclerosis is ameliorated, the causative role of inflammation in atherosclerosis remains a hypothesis.

• #1 An insight into pathogenesis of cardiovascular diseases

  https://www.oatext.com/An-insight-into-pathogenesis-of-cardiovascular-diseases.php

  Chronic psychosocial stress plays a key role in the pathogenesis of vascular diseases (both cardiovascular diseases and disorders of micro vascular circulation), which when severe in intensity, accelerates the inflammation, increasing morbidity and mortality especially, when multiple conditions are present together such as depression, rheumatoid arthritis, NAFLD and several other disorders, including traditional risk factors. […] Cardiovascular diseases and disorders of micro vascular circulation (e. rheumatoid arthritis and non alcoholic fatty liver disease) develop in parallel, lending support to the hypothesis that, they share a common pathophysiologic mechanism, which is stress induced, lipid mediated vascular inflammation.

• #1 Depression, anxiety and stress linked to poor heart health in two new studies | American Heart Association

  https://newsroom.heart.org/news/depression-anxiety-and-stress-linked-to-poor-heart-health-in-two-new-studies

  Depression and anxiety may accelerate the onset of risk factors for increased heart attack and stroke, according to a Boston-based study. […] A separate study based in Dallas found that cumulative stress contributed to health behaviors such as smoking that negatively affect cardiovascular health and potentially increasing plaque buildup in the arteries and other known cardiovascular disease risk factors. […] Mental health conditions, including depression, anxiety and stress are known to increase the risks for poor heart health, according to the American Heart Association and in two new studies, researchers measured how much ones mental state affects heart health. […] There are clear associations between psychological health and cardiovascular disease risk. […] The first study examined the mechanism by which the mental state affects heart health. Researchers found that anxiety and depression sped the development of new cardiovascular disease risk factors.

• #1 Depression, anxiety and stress linked to poor heart health in two new studies | American Heart Association

  https://newsroom.heart.org/news/depression-anxiety-and-stress-linked-to-poor-heart-health-in-two-new-studies

  The analysis also indicates that ongoing stress raised the risk of poor heart and brain health in two ways: by directly influencing physical well-being, as well as increasing poor lifestyle behaviors such as smoking and being sedentary, which, in turn, lead to reduced cardiovascular health. […] Previous research has shown that chronic stress can lead to elevated levels of stress hormones like cortisol, which, in turn, can affect blood sugar levels, inflammation and other biological chain reactions that impact the heart.

• #1 Link Between Depression and Heart Failure in US Veterans Uncovered

  https://bioengineer.org/link-between-depression-and-heart-failure-in-us-veterans-uncovered/

  From a pathophysiological standpoint, several mechanisms might underpin the observed association. Chronic depression has been linked to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to sustained elevations in cortisol levels which can promote adverse cardiac remodeling. […] Additionally, depression is associated with pro-inflammatory states and heightened sympathetic nervous system activity, both of which contribute to the development and progression of heart failure. […] Importantly, the consistency of increased heart failure incidence among depressed veterans, despite their otherwise low cardiovascular risk profile, signals that depression transcends being merely a marker of poor health. Instead, it may serve as an active driver of pathogenesis. […] This insight elevates the clinical urgency to intervene at the psychological level early in the course of disease, potentially averting cardiac deterioration and improving overall outcomes.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  Many of the characteristic cellular responses found in HF can be activated by oxidative stress, including cellular hypertrophy, changes in gene expression, and cell death. […] The chronic low-grade, systemic and local inflammation that develops during obesity links obesity to the development of insulin resistance, which then effects a variety of different organs involved in the control of metabolic homeostasis, including adipose tissue, liver, endocrine pancreas, hypothalamus, and possibly skeletal muscle. […] The pathways that trigger the cellular phenotypes of hypertrophy and apoptosis appear to involve stress-responsive protein kinases such as mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinases, and p38 MAPKs in the myocardium, many of which are activated by reactive oxygen species (ROS).

• #1 Cardiovascular disease

  https://www.nhs.uk/conditions/cardiovascular-disease/

  Cardiovascular disease (CVD) is a general term for conditions affecting the heart or blood vessels. […] It’s usually associated with a build-up of fatty deposits inside the arteries (atherosclerosis) and an increased risk of blood clots. […] High blood pressure (hypertension) is one of the most important risk factors for CVD. If your blood pressure is too high, it can damage your blood vessels. […] Smoking and other tobacco use is also a significant risk factor for CVD. The harmful substances in tobacco can damage and narrow your blood vessels. […] Cholesterol is a fatty substance found in the blood. If you have high cholesterol, it can cause your blood vessels to narrow and increase your risk of developing a blood clot. […] High blood sugar levels can damage the blood vessels, making them more likely to become narrowed.

• #1 Analyzing CHD risk factors and constructing a predictive model to eval | VHRM

  https://www.dovepress.com/constructing-a-predictive-model-to-evaluate-the-risk-of-chd-based-on-n-peer-reviewed-fulltext-article-VHRM

  Accompanied by hyperthyroidism, the consequent overproduction of thyroid hormones, there may be an elevation in heart rate and myocardial contractility, over time, this could impose a greater workload on the heart and heighten the risk of CHD. […] Chronic hypertension can lead to damage in the blood vessel walls, elevating the risk of arteriosclerosis and consequently increasing the risk of CHD. […] Both stroke and CHD involve the narrowing or blockage of blood vessels, the underlying mechanisms, such as atherosclerosis (the buildup of plaques in the arteries), are similar in both conditions. […] This increased risk is attributed to the systemic inflammation caused by COPD, which can lead to atherosclerosis, the primary cause of CHD.

• #1 New Garland/Dora group paper provides a novel mechanism for the vasospasm underlying cardiovascular disease — Department of Pharmacology

  https://www.pharm.ox.ac.uk/news/new-garland-dora-group-paper-provides-a-novel-mechanism-for-the-vasospasm-underlying-cardiovascular-disease

  The Vascular Pharmacology group has published a paper in Hypertension showing that loss of nitric oxide production by endothelial cells, a ubiquitous feature of cardiovascular disease, raises the electrical excitability of arterial smooth muscle by recruiting T-type voltage-gated calcium channels. This change switches physiological vasomotion to pathological vasospasm. […] Endothelial dysfunction in small arteries is a ubiquitous, early feature of cardiovascular disease, including hypertension. […] Therefore, in myogenic and nonmyogenic small arteries, reduced NO bioavailability engages T-type VGCCs, triggering transient depolarizing spikes in normally quiescent vascular smooth muscle to cause vasospasm. T-type block may offer a means to suppress vasospasm without inhibiting myogenic tone mediated by L-type VGCCs.

• #1 Biomedicines | Topical Collection : Cardiovascular Disease: From the Pathogenesis to Novel Therapeutic Approaches

  https://www.mdpi.com/journal/biomedicines/special_issues/Cardiovascular_Disease_Pathogenesis

  Cardiovascular Disease: From the Pathogenesis to Novel Therapeutic Approaches […] Identifying and treating the rupture-prone atherosclerotic plaque remains a challenge for reducing the burden of cardiovascular diseases (CVDs). CVDs, a major cause of mortality in humans, have a complex etiology. Multiple risk factors and pathological mechanisms contribute to this disease, including metabolic perturbations in cardiomyocytes and endothelial cells. A broad study of the pathogenetic mechanisms of the CVD onset and progression has focused on the importance of endothelial dysfunction (ED) and macrophage activation in these processes. […] In T2DM, energy metabolism is greatly reshaped due to a deregulation of glucose and fatty acid metabolism, and insulin resistance is recognized as an important mechanism for cardiovascular dysfunction. […] Therefore, the measurement of metabolic changes might have a huge impact on the discovery of clinical and pharmacological biomarkers. […] The metabolic shifts are pivotal for monocyte and macrophage function as well. Contact with atherogenic particles such as oxidized phospholipids prime to a regulatory metabolic pro-inflammatory phenotype, orchestrated via pattern-recognition receptors, nuclear receptors, and other transcription factors; therefore, metabolic changes in endothelial cells, monocytes, and macrophages may have a deep effect on the inflammatory phenotype of these cells, determining their impact on the advancement of atherosclerosis. […] As inflammation and metabolic shifts are closely entwined in both immune cells as well as endothelial cells, therapeutic targets aiming at altering the cellular metabolism of activated cells may hold great potential in the treatment of cardiovascular patients. […] However, to identify appropriate therapeutic targets that could help to design disease-modifying agents, a comprehensive analysis of the transcriptome and metabolome of atherosclerotic plaque and associated cells is needed. […] The pivotal concept is based on the relationship between cell metabolism, the regulation of immune-metabolic homeostasis, and cardiovascular disease.

• #1 Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01055-2

  Histone modification is one of the important regulatory mechanisms in epigenetics. Abnormal histone modification results in an imbalance in the expression of genes associated with cardiovascular disease, resulting in changes in cellular phenotypes and cardiac function. Key molecules of histone modification (histone methylation and histone acetylation) may lead to the occurrence and progression of cardiovascular disease through their influence on cardiovascular pathophysiological pathways. […] Cardiovascular disease can also be regulated by histone methylation. […] Histone deacetylase inhibitors are deemed as underlying drugs and strategies for the treatment of myocardial infarction and ischemiareperfusion injury. […] Histone acetylation is crucial to the treatment of atherosclerosis. […] Noncoding RNAs play an important regulatory role in complex life processes and can be considered as a potential therapeutic target for many cardiovascular diseases.

• #1 What is Cardiovascular Disease? | American Heart Association

  https://www.heart.org/en/health-topics/consumer-healthcare/what-is-cardiovascular-disease

  Heart failure, sometimes called congestive heart failure, means the heart isn’t pumping blood as well as it should. Heart failure does not mean that the heart stops beating — that’s a common misperception. Instead, the heart keeps working, but the body’s need for blood and oxygen isn’t being met. […] An arrhythmia can affect how well your heart works. With an irregular heartbeat, your heart may not be able to pump enough blood to meet your body’s needs. […] When heart valves don’t open enough to allow the blood to flow through as it should, a condition called stenosis results. When the heart valves don’t close properly and thus allow blood to leak through, it’s called regurgitation. […] The medications prescribed after a cardiovascular event can aid in recovery and help prevent another heart attack or stroke.

• #1 Cardiovascular Disease: Types, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/21493-cardiovascular-disease

  Many people enjoy a high quality of life and can manage their cardiovascular disease with the help of their healthcare team. Your chances for a positive outcome are higher if you engage in your healthcare and follow your providers treatment plan. Its important to take medications exactly as prescribed. […] Cardiovascular diseases are conditions that affect your heart and blood vessels. Without appropriate treatment, heart disease can lead to heart attacks or strokes. You can make lifestyle changes or take medications to manage cardiovascular disease. Earlier diagnosis can help with effective treatment. Many people live a full and active life with a cardiovascular disease.

• #1

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  The complex physiological signal transduction networks that respond to the dual challenges of inflammatory and oxidative stress are major factors that promote the development of cardiovascular pathologies. […] Inhibition and/or attenuation of these signaling networks also delays the onset of disease. […] Therefore, a concept of targeting the signaling networks that are involved in inflammation and oxidative stress may represent a novel treatment paradigm for many types of heart disease. […] Inflammation and oxidative stress are well known to promote HF phenotypes. […] The processes of inflammation and oxidative stress are through physiological interactions to the activation of downstream networks that in turn promote various human pathologies, including aging, carcinogenesis, neurodegenerative disorders, and HF associated with various causes and phenotypes.

• #1 Pipeline – AstraZeneca

  https://www.astrazeneca.com/our-therapy-areas/pipeline.html

  AZD1705 – Phase I […] Mechanism: lipid lowering […] Area under investigation: cardiovascular disease […] Date commenced phase: Q1 2024 […] Molecule size: Small molecule […] […] […] AZD4144 – Phase I […] Mechanism: inflammation modulator […] Area under investigation: cardiorenal disease […] Date commenced phase: Q4 2023 […] Molecule size: Small molecule […] […] […] AZD3427 – Phase II […] Mechanism: relaxin mimetic […] Area under investigation: heart failure […] Date commenced phase: Q2 2023 […] Molecule size: Large molecule […] […] […] balcinrenone/dapagliflozin – Phase III […] Mechanism: MR modulator + SGLT2 inhibitor […] Area under investigation: heart failure with CKD […] Date commenced phase: Q2 2024

• #1 Mounjaro, Zepbound weight loss drugs may help lower blood pressure

  https://www.medicalnewstoday.com/articles/hypertension-mounjaro-zepbound-weight-loss-drugs-may-help-lower-blood-pressure

  Researchers say people who took tirzepatide saw a significant reduction in their blood pressure over 36 weeks. […] Tirzepatide, which is prescribed for type 2 diabetes (Mounjaro) and obesity (Zepbound), is being studied for its effects on cardiovascular conditions as well. […] Due to well-established links between obesity and cardiovascular conditions, researchers are taking a closer look at how tirzepatide and similar drugs, such as semaglutide (Ozempic and Wegovy), known as GLP-1 RAs can impact heart health. […] Additionally, it is also unclear from the research whether blood pressure decreased solely due to weight loss or if there was an additional mechanism at work due to the medication. […] Questions persist regarding whether the observed effects on blood pressure are attributed solely to weight loss or if the drug itself plays a direct role.

• #1 Mounjaro, Zepbound weight loss drugs may help lower blood pressure

  https://www.medicalnewstoday.com/articles/hypertension-mounjaro-zepbound-weight-loss-drugs-may-help-lower-blood-pressure

  It’s certainly at least mostly a blood pressure effect. It could be that there’s some direct effect of the drug, said Dr. James de Lemos, a study author and a professor in the Department of Internal Medicine and Chief of the Division of Cardiology at UT Southwestern Medical Center in Texas. […] For individuals with obesity and diabetes, the findings could show promise in tackling a host of serious co-morbidities such as metabolic syndrome. […] We’re entering an era for the first time where pharmacologic treatment of obesity and diabetes may yield tangible benefits in terms of long-term cardiac outcomes, said de Lemos.

• #1 BBC Audio | Health Check | Shingles vaccine lowers risk of heart disease

  https://www.bbc.com/audio/play/w3ct6vj7

  Receiving a specific type of shingles vaccine may provide a 23% lower risk of cardiovascular events like stroke or heart failure for up to 8 years. […] scientists are trying to understand the mechanism underlying these unintended benefits.

• #1 Shingles vaccine lowers heart attack risk for 8 years, says new study: Here’s what it means for you | Health and Wellness News – The Indian Express

  https://indianexpress.com/article/health-wellness/shingles-vaccine-heart-attack-risk-study-9987728/

  People who have been vaccinated against shingles have a 23% lower risk of cardiovascular conditions — with the risk for heart attacks being 22% lower and heart failure 26% lower, according to a large study from South Korea. […] The study found the risk of overall cardiovascular events was 23% lower in people who had received the vaccine. The risk of a major cardiovascular event was 26% lower, heart failure 26% lower, disorders that affect the blood flow in the brain such as strokes was 24% lower, heart attack was 22% lower, and clotting disorder was 22% lower. […] While the mechanism of action is not entirely understood, scientists think it could be because the vaccines prevent shingles, which has been associated with an increased risk of cardiovascular diseases. Previous studies have shown that an infection increased the risk of conditions like heart attack and heart failure by 1.5 to 2 fold. […] A shingles infection can cause blood vessel damage, inflammation and clot formation that can lead to heart disease. By preventing shingles, vaccination may lower these risks.

• #2 DOAJ Logotype

  https://doaj.org/article/46db1dc33f4e4ecdb68488cb7eb03084

  Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. […] This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. […] Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. […] However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

• #2 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. […] Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. […] Atherosclerosis is the main cause of cardiovascular-related death worldwide. It is a thickening and hardening of the arterial wall, accompanies aging, and is related to major adverse impact on the cardiovascular system and various other diseases. Elevated plasma cholesterol level (>150 mg/dL) is a major cause of the development of atherosclerosis.

• #2 Pathology of cardiovascular system | PPT

  https://www.slideshare.net/slideshow/pathology-of-cardiovascular-system-192305341/192305341

  The most common cause of IHD is luminal narrowing of the C.A. by atherosclerosis and the following contributing factors: Acute plaque changes Coronary artery thrombosis Coronary artery vasospasm. […] Atherosclerosis is a disease characterized by the buildup of plaque in artery walls. It begins with endothelial cell injury from risk factors like high cholesterol. This allows immune cells like monocytes to enter the artery wall and become lipid-filled foam cells. Over time, a fatty streak or atherosclerotic plaque forms and grows within the artery wall. Advanced plaques can rupture, causing blood clots that block blood flow and lead to heart attacks, strokes, or other complications. […] Atherosclerosis is a progressive inflammatory disease where fatty deposits called atheromas build up in the arteries. Over time it can restrict blood flow and cause complications like heart attacks or strokes. It begins early in life with fatty streaks in the arteries. Clinical symptoms often do not appear until later in life. Key risk factors include age, smoking, high blood pressure, high cholesterol, diabetes, obesity, lack of exercise, diet, stress, alcohol use, and family history.

• #2 What is Cardiovascular Disease? | American Heart Association

  https://www.heart.org/en/health-topics/consumer-healthcare/what-is-cardiovascular-disease

  Cardiovascular disease can refer to a number of conditions: […] Heart and blood vessel disease, also called heart disease, includes numerous problems, many of which are related to atherosclerosis. […] Atherosclerosis is a condition that develops when a substance called plaque builds up in the walls of the arteries. This buildup narrows the arteries, making it harder for blood to flow through. If a blood clot forms, it can block the blood flow. This can cause a heart attack or stroke. […] A heart attack occurs when the blood flow to a part of the heart is blocked by a blood clot. If this clot cuts off the blood flow completely, the part of the heart muscle supplied by that artery begins to die. […] An ischemic stroke, which is the most common type of stroke, occurs when a blood vessel that feeds the brain gets blocked, usually from a blood clot.

• #2 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  CAD is caused primarily by plaque formation within the intima of the vessel wall, with plaque being defined as a fatty material growing inside intima along with a severe inflammation, especially if the inflammation is chronic. […] As a result, atherosclerotic plaque may erode or rupture, initially resulting in thrombosis and then a closure of the vessel, leading to myocardial infarction, stroke, limb ischemia, and death. […] Endothelial dysfunction in modern cardiovascular medicine is described as changes in the production and availability of endothelial-derived NO, prostacyclin, and endothelin, as well as their impact on vascular reactivity. […] The endothelial membrane is permeable to compounds such as NO and H2O2, which causes the activation of the transcription factors and protease.

• #2 Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  https://www.mdpi.com/2227-9059/10/8/1938

  Endothelial dysfunction is considered to be the earliest marker of atherosclerosis and, in effect, CAD. […] The expression of the nicotinamide adenine dinucleotide phosphate oxidase in the vessel wall with the consequent overproduction of NO has been proposed as an initial step in the chronic dysregulation of normal NO production by eNOS, which is characteristic of the monomeric forms of eNOS. […] Taking this into account, the endothelial dysfunction is directly related to a decreased production and sensitivity of cells to NO. […] Inflammation in diseases such as polyarteritis nodosa and cryoglobulinemia is driven by IC deposition (antibody-mediated IC formation, microaneurysms). […] The underlying pathogenesis involves many mechanisms such as cell-mediated inflammation, immune complex (IC)-mediated inflammation, and ANCA-mediated inflammation.

• #2 Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases – Université Savoie Mont Blanc

  http://catalogue.univ-smb.fr/discovery/fulldisplay?docid=cdi_proquest_miscellaneous_1975593420&context=PC&vid=33USMB_INST:USMB&lang=fr&search_scope=MyInst_and_CI&adaptor=Primo%20Central&tab=ALL&query=creator%2Ccontains%2CWang%2C%20Xianwei&offset=0

  NLRP3 inflammasome is a key multiprotein signaling platform that tightly controls inflammatory responses and coordinates antimicrobial host defenses by activating caspase-1 for the subsequent maturation of pro-inflammatory cytokines, IL-1β and IL-18, and induces pyroptosis. The assembly and activation of NLRP3 inflammasome are linked to the pathogenesis of several cardiovascular disease risk factors, such as hypertension and diabetes, and their major consequences—myocardial remodeling. The study of the NLRP3 inflammasome in these cardiovascular disease states may uncover important triggers and endogenous modulators of the disease, and lead to new treatment strategies. This review outlines current insights into NLRP3 inflammasome research associated with cardiovascular diseases and discusses the questions that remain in this field.

• #2

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  By contrast, M2 macrophages exhibit an anti-inflammatory, pro-regenerative phenotype due to their capacity to secrete high levels of anti-inflammatory cytokines, including IL-10 and certain growth factors. […] The pathological processes in many disease models are fueled by macrophage-derived cytokines. […] The mechanisms by which myocardial oxidative stress might impair cardiac function is probably oxidative damage to cellular proteins and membranes, thereby inducing cellular dysfunction or death through apoptosis and/or necrosis. […] ROS may also activate signaling pathways that contribute to ischemic preconditioning, cardioprotection, and myocardial damage, and high levels of ROS induce structural modifications of the sarcomere that impact pump function and the general pathogenesis of HF.

• #2 Immunity, atherosclerosis and cardiovascular disease | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-117

  The major risk factors which can be modified for atherosclerosis (and CVD) are hypertension, smoking, diabetes and dyslipidemia. […] OxLDL could play a role both in atherogenesis and in plaque complications. […] The proinflammatory and immune stimulatory effects of oxLDL are mimicked by inflammatory phospholipids, such as lysophosphatidylcholine (LPC), which is a major phospholipid in atherosclerotic lesions. […] The role of cell death as a cause of inflammation in atherosclerosis and plaque rupture is complicated and depends most likely on stage of disease, and naturally, on whether cell death is organized as in apoptosis, or not, as in necrosis. […] Dying cells can activate the innate immune system and induce an inflammatory response with release of the proinflammatory cytokine IL-1beta, activating the inflammasome.

• #2 Depression, anxiety and stress linked to poor heart health in two new studies | American Heart Association

  https://newsroom.heart.org/news/depression-anxiety-and-stress-linked-to-poor-heart-health-in-two-new-studies

  While it is known that depression and anxiety increase the risk of cardiovascular disease, such as heart attack and stroke, the mechanism underlying this is not completely known. […] In our study, we identified a mechanism that appears to largely account for the link between these psychological factors and cardiovascular disease. […] Researchers suggest that depression and anxiety might induce brain changes that trigger downstream effects in the body, such as increased inflammation and fat deposition. […] The findings emphasize the importance of screening for cardiovascular risk factors among people with depression and anxiety. […] This study illustrates that health care professionals should be aware that negative psychological health things like depression or anxiety not only affect patients mental state of being, but also can impact their physical health and the risk for heart disease.

• #2

  https://link.springer.com/article/10.1007/s12551-020-00742-0

  The significance of inflammation in the development of HFpEF was firmly established in a swine model following induction of the three most common inflammation-associated comorbidities in HFpEF patients: arterial hypertension, diabetes mellitus, and hypercholesterolemia. […] The chronic low-grade, systemic and local inflammation that develops during obesity links obesity to the development of insulin resistance, which then effects a variety of different organs involved in the control of metabolic homeostasis, including adipose tissue, liver, endocrine pancreas, hypothalamus, and possibly skeletal muscle. […] These findings suggest that modulation of titin-based stiffness via cGMP-enhancing therapy could be a useful approach to correcting pathologically elevated LV diastolic stiffness, one of the primary characteristics of HFpEF in patients.

• #2 Pipeline – AstraZeneca

  https://www.astrazeneca.com/our-therapy-areas/pipeline.html

  […] […] baxdrostat/dapagliflozin – Phase III […] Mechanism: aldosterone synthase inhibitor and reversible inhibitor of SGLT2 […] Area under investigation: prevention of heart failure […] Date commenced phase: Q1 2025 […] […] […] Wainua – Phase III […] Mechanism: ligand-conjugated antisense […] Area under investigation: patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) […] […] […] zibotentan/dapagliflozin – Phase III […] Mechanism: endothelin A receptor antagonist/SGLT2 inhibitor […] Area under investigation: CKD with high proteinuria […] Date commenced phase: Q4 2023

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