Materiały źródłowe

• #1 Pathogenesis, Diagnosis and Treatment of the Cerebral Aneurysm

  https://www.iomcworld.org/open-access/pathogenesis-diagnosis-and-treatment-of-the-cerebral-aneurysm-83456.html

  An intracranial aneurysm, also known as a brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel. […] Aneurysm means an outpouching of a blood vessel wall that is filled with blood. Aneurysms occur at a point of weakness in the vessel wall. This can be because of acquired disease or hereditary factors. The repeated trauma of blood flow against the vessel wall presses against the point of weakness and causes the aneurysm to enlarge. […] Both high and low wall shear stress of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall).

• #1 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta. […] The pathogenic mechanisms and therapeutic targets for aortic aneurysms have been examined over the past decade; however, there are unknown pathogenic mechanisms involved in cellular heterogeneity and plasticity, the complexity of the transforming growth factor- signaling pathway, inflammation, cell death, intramural neovascularization, and intercellular communication. […] Aortic rupture is not only associated with increasing aneurysm diameters but also results from characteristic changes, which involve the progressive expansion and weakening of the three layers of the aorta: the intima, media, and adventitia. […] Multiple pathological processes, including extracellular matrix (ECM) breakdown, inflammation, phenotype switching of vascular smooth muscle cells (SMCs), oxidative stress, and neovascularization, contribute to this process.

• #1 Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

  https://www.oaepublish.com/articles/2347-8659.154433/

  Intracranial aneurysms are a life-threatening cerebrovascular pathology with a probability of spontaneous rupture. Recent investigation has reinforced inflammation’s role in the pathophysiological process of cerebral aneurysms. The majority of evidence from intensive investigation has implicated a mounting inflammatory response during the aneurysm pathogenesis. Hemodynamic insult is considered to be one of the first steps in activating the cerebral vessel walls’ inflammatory response. Upon the hemodynamic insult, this balance is perturbed, leading to vessel wall weakening. Dilation results, as extracellular matrix is degraded by increased levels of matrix metalloproteinases (MMP) compounded by concomitant apoptotic death of vascular smooth muscle cells (VSMCs). Integral disturbances lead to less organization within the aneurysm wall and fewer distinct layers. Simultaneously, MMP activation has been found to facilitate flow-induced internal elastic lamina (IEL) fragmentation. Vascular smooth muscles cells (VSMCs), mainly found in the media layer, are recognized as major producers of matrix in the vessel wall. Upon endothelial injury, intimal thickening occurs as VSMCs migrate into the intima and proliferate. Phenotypic transformation is seen in these migrated VSMCs as environmental change induces a switch from a contractile phenotype to a synthetic pro-inflammatory matrix remodeling phenotype in these cells. Endothelial cells are also affected by the hemodynamic insult. Experimentally, endothelial cells respond to hemodynamic stress with the up-regulation of the inflammatory mediator, prostaglandin E receptor 2 (EP2), during the formation of cerebral aneurysms. As cerebral vessel walls undergo change during aneurysm development, the formation of new vessels, angiogenesis, also contributes to aneurysmal progression. Angiogenesis indirectly advances the inflammatory process of aneurysm progression by aiding in the delivery of inflammatory cells to vessel walls. Human and animal studies have both shown that inflammatory cells and mediators are involved in IA pathogenesis. A number of these inflammatory cells and mediators are highlighted in this section, with a special focus on the most recent investigation. T cells and macrophage infiltration have been found to be associated with human cerebral aneurysm rupture. The role of the inflammatory mediators, chemokines, has been studied in aneurysm formation. These data indicate that inflammatory cells are being actively recruited to the aneurysm wall as a result of high chemokine levels, further contributing to IA formation and eventual rupture. Intensive investigation has implicated the inflammation in the complex pathophysiological processes that underlie IA development, progression, and rupture.

• #1 Innovation in pathogenesis and management of aortic aneurysm

  https://www.wjgnet.com/2220-315x/abstract/v14/i2/91408.htm

  Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor , interleukin-1, tumor necrosis factor-, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. […] In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

• #1 Pathogenesis of Aortic Aneurysms – Mechanisms of Vascular Disease – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534278/

  Patients with AAAs frequently have generalized atherosclerosis, and numerous studies show the association of coronary and peripheral atherosclerosis with AAA. […] The most compelling argument for a causative role of atherosclerosis in AAA has been centered on arterial remodeling. […] On the basis that atherosclerosis stimulates AAA development, all patients with AAA would necessarily have significant atherosclerosis and thus should be considered for indicated medical therapy, as currently advised by American Heart Association guidelines in which AAA is considered an atherosclerotic equivalent. […] Current evidence implicates both innate and adaptive immunities in AAA pathogenesis. […] Overall it is possible from current data that both Th1 and Th2 responses are involved in AAA pathogenesis.

• #1 Aneurysm – Wikipedia

  https://en.wikipedia.org/wiki/Aneurysm

  Aneurysms form for a variety of interacting reasons. Multiple factors, including factors affecting a blood vessel wall and the blood through the vessel, contribute. […] The pressure of blood within the expanding aneurysm may also injure the blood vessels supplying the artery itself, further weakening the vessel wall. Without treatment, these aneurysms will ultimately progress and rupture. […] A mycotic aneurysm is an aneurysm that results from an infectious process that involves the arterial wall. A person with a mycotic aneurysm has a bacterial infection in the wall of an artery, resulting in the formation of an aneurysm. One of the causes of mycotic aneurysms is infective endocarditis. […] The third stage of syphilis also manifests as aneurysm of the aorta, which is due to loss of the vasa vasorum in the tunica adventitia.

• #1 The mechanism and therapy of aortic aneurysms | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01325-7

  Aortic aneurysm is a chronic aortic disease affected by many factors. […] Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm, the specific mechanisms remain unclear. […] The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. […] Aneurysms rupture when the dilated wall of an artery cannot support the stress created by the flow of blood inside. […] The exact cause of the disease is still unknown, but a widely proposed hypothesis has been that specific changes in the hemodynamic forces acting on the aortic walls are a key contributor to the origin and progression of the disease. […] Vascular smooth muscle cells (VSMCs) are the major component of the vessel wall and perform many functions while maintaining the vascular structure. The various changes in VSMCs are an important cause of AA formation.

• #1 Cerebral Aneurysm: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1161518-overview

  Cerebral aneurysms are pathologic focal dilatations of the cerebrovasculature that are prone to rupture. […] The pathogenesis of cerebral aneurysms is related inherently to structural aberrations of the cerebrovasculature, although the etiology of these abnormalities may be diverse. The integrity of the internal elastic lamina is compromised, with associated elastic defects in the adjacent layers of the tunica media and adventitia. Muscular defects of the tunica media and minimal support of adjacent brain parenchyma augment the pathologic potential of chronic hemodynamic stress on the arterial wall. Focal turbulence and discontinuity of the normal architecture at vessel bifurcations may account for the propensity of saccular aneurysm formation at these locations. Distal aneurysms may be smaller compared with proximal sites, yet the risk of rupture may be dissimilar due to the relatively thinner parent artery wall thickness.

• #1 Pathogenesis of Aortic Aneurysms – Mechanisms of Vascular Disease – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534278/

  Examination of biopsies of large human AAAs indicates marked medial thinning and deficiency of VSMCs as consistent features. […] Loss of functional elastin is an important feature of human AAA and may be a more generalized feature of arteries of patients with aneurysms. […] The mechanism by which alterations of TGF promotes AAA in these pre-clinical studies is currently controversial since the effects of blocking this cytokine varies in different models. […] The development of aneurysms in which infection is a primary pathogen is well documented albeit rare. […] One of the suggested reasons for the focal nature of AAA formation has been the variation in haemodynamic forces throughout the aorta. […] New vessel formation has been demonstrated within the adventitia of human AAA biopsies and implicated in promoting influx of inflammatory cells.

• #1 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Although the pathological mechanisms of aortic aneurysms have been defined, there are no effective drugs to treat aortic aneurysm growth or rupture. […] The loss of structural integrity due to vascular SMC dysfunction, including apoptosis and ECM degradation, leads to weakness and dilatation of the aortic wall, which are hallmarks of aortic aneurysm. […] An imbalance in reparative/ECM production and inflammatory/ECM degradation in SMCs that underwent phenotypic switching and are known as synthetic SMCs in response to constant pathological stimuli damages the aortic wall, leading to dilatation and rupture in aortic aneurysms. […] The components of the transforming growth factor- (TGF-) signaling pathway, including receptors and SMAD proteins, are fundamental for synthesizing SMC contractile proteins, ECM proteins, elastin, and collagen.

• #1 Intracranial Aneurysm Development 101: Pathogenesis and Risk Factors

  https://consultqd.clevelandclinic.org/intracranial-aneurysm-development-101-pathogenesis-and-risk-factors

  Evidence mounts that inflammation plays a key role […] Recently, increased focus has been placed on the role of inflammation in causing vascular smooth muscle dysfunction, driving both aneurysm formation and rupture, especially in vulnerable individuals. […] The role of inflammation in aneurysm pathogenesis is an important focus of research. Current evidence points to a complex interplay between endothelial dysfunction, inflammatory responses and flow dynamics that eventually leads to aneurysm rupture. […] Areas of vessel dysfunction or injury attract macrophages, mast cells and T cells, which then contribute to alteration of vascular smooth muscle cells. As macrophages release cytokines and other mediators, matrix metalloproteinases cleave the extracellular matrix, inducing a positive feedback cycle that further promotes migration of inflammatory cells.

• #1

  https://www.jci.org/articles/122

  Abdominal aortic aneurysm (AAA), an inflammatory disease, involves leukocyte recruitment, immune responses, inflammatory cytokine production, vascular remodeling, neovascularization, and vascular cell apoptosis, all of which contribute to aortic dilatation. […] This study demonstrates that mast cells, key participants in human allergic immunity, participate in AAA pathogenesis in mice. […] Mast cell-deficient KitW-sh/KitW-sh mice failed to develop AAA elicited by elastase perfusion or periaortic chemical injury. […] Activation of mast cells in WT mice via C48/80 injection resulted in enhanced AAA growth while mast cell stabilization with disodium cromoglycate diminished AAA formation. […] Mechanistic studies demonstrated that mast cells participated in angiogenesis, aortic SMC apoptosis, and matrix-degrading protease expression. […] These results demonstrate that mast cells participate in AAA pathogenesis in mice by releasing proinflammatory cytokines IL-6 and IFN-, which may induce aortic SMC apoptosis, matrix-degrading protease expression, and vascular wall remodeling, important hallmarks of arterial aneurysms.

• #1 Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018679

  Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. […] Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. […] Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. […] Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. […] In the present study, we hypothesized that repeated retention of P. gingivalis by the ILT of AAA could enhance neutrophil recruitment and subsequent activation, and thus participate in aneurysmal progression.

• #1 The mechanism and therapy of aortic aneurysms | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01325-7

  Cytokines play an important role in AA. Cytokines are mainly secreted by immune cells and affect the level of inflammation in vascular tissue and the degradation of ECM. […] ROS and oxidative stress play an important role in the formation of AA, and a rise in oxidative stress has been observed in both patients and mice. […] The production of ROS is dependent on NOX, uncoupled eNOS (also known as NOS3), mitochondria and xanthine oxidase (XO).

• #1 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  The pathophysiology of IAs is complex. Although many factors play together in the formation, progression, and rupture of IAs, the research hitherto suggests that inflammation heavily contributes to IAs from formation to rupture. The endothelial dysfunction, smooth muscle cells (SMCs) phenotypic switching, infiltration and accumulation of inflammatory cells in the arterial walls, and the expression and release of pro-inflammatory cytokines such as interleukin (IL) -1β, and tumor necrosis factor-alpha (TNF-α), chemokines such as monocyte chemoattractant protein-1 (MCP-1), and IL-8, cell adhesion molecules, namely, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and extracellular matrix remodeling proteinases such as MMPs including MMP-2 and MMP-9 have been implicated in IA formation and rupture. The expression of these pro-inflammatory markers and MMPs is regulated by NF-κB transcription activity.

• #1 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture.

• #1 175 PATHOGENESIS OF ABDOMINAL AORTIC ANEURYSMS: THE ROLE OF METALLOPROTEINASES AND THEIR INHIBITORS | Heart

  https://heart.bmj.com/content/99/suppl_2/A100.2

  An abdominal aortic aneurysm (AAA) represents a complex pathophysiological process of weakening and dilatation of the aortic wall, which is associated with atherosclerosis, a chronic inflammatory response and hemodynamic alterations. […] Degradation of the extracellular matrix by the matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs), as well as the production of reactive oxygen species, have fundamental roles in the development of AAA. […] The exact pathogenetic mechanisms remain incompletely elucidated. […] The inflammatory process associated with turbulent intraluminal flow most likely causes endothelial dysfunction that creates a milieu favorable to the release of MMPs. […] The MMPs cause massive destruction of elastin fibers which significantly remodels the arterial wall, resulting in dilatation and AAA formation.

• #1 The mechanism and therapy of aortic aneurysms | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01325-7

  The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] Among the MMP family, MMP-2/9 is the most studied matrix metalloproteinase. High levels of MMP-2/9 expression can be observed in AA tissue. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] Autophagy is a lysosome-mediated process that removes damaged proteins and organelles. […] The immune response plays an important role in the course of AA. […] Immune cells not only secrete inflammatory factors that lead to apoptosis of aortic wall cells and VSMC phenotype switching but also secrete proteases that induce ECM degradation and lead to aortic dilation and rupture.

• #1 Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

  https://www.mdpi.com/2073-4409/13/3/274

  Overactive matrix metalloproteinases (MMPs) family proteins play a major role in AAA pathogenesis, especially MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14. […] Another hallmark of AAA is a strong inflammation, engaging immune cells as well as inflammatory pathway activation, like FOS and interleukine-17 (IL-17), interleukin-1β (IL-1β) and nuclear factor κB (NF-κB). […] The interplay of infiltrated inflammatory cells is complex in forming the inflammatory environment during AAA development. […] The action of even one of the factors described above causes a cascade of degradation and a weakening of the aortic wall, weaving a complex network of AAA pathogenesis and development, influencing pathways of molecular factors.

• #1 Etiology and Pathogenesis of Aortic Aneurysm | IntechOpen

  https://www.intechopen.com/chapters/44127

  The action of proteolytic enzymes, notably matrix metalloproteases and serine proteases, has been associated with the destruction of the extracellular matrix. […] Aortic aneurysm is a multifactorial disease, with both genetic and environmental risk factors contributing in variable degrees to the underlying pathobiology, leading to proteolytic degradation of aortic wall components, stresses within the aortic wall, and variable intervention of inflammation and/or autoimmune response. […] Numerous research data provide valuable mechanistic insight into the genetic, environmental, and mechanistic pathogenesis of aortic aneurysm, reveal diagnostic markers, and identifies new therapeutic targets, such as recently described theranostic approaches.

• #1

  https://apcz.umk.pl/JEHS/article/view/41015

  Abdominal aortic aneurysms (AAA) affect 2.4% of the population, with men being five times more likely to be affected than women. The development of AAA is linked to changes in the elastin and vascular wall collagen. The enzymes that damage the cell wall are called metalloproteinases. AAA forms as a result of damage to elastic fibres and the loss of the property of reversible deformation of the aortic wall. The degradation of elastin and other stem proteins in the aortic wall is caused by metalloproteinases and serine proteases, accompanied by cysteine proteases and asparagine proteases. Increased calprotectin levels are observed in AAA patients in comparison to patients with a healthy aorta. A significant role in the pathogenesis of AAA and its rupture is played by inflammatory response cells; proteases of the tissue plasma coagulation and fibrinolysis.

• #1 Pathogenesis of Aortic Aneurysms – Mechanisms of Vascular Disease – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534278/

  The volume of thrombus is closely correlated to the size of the AAA suggesting that the thrombus could simply be a result of the changes in flow pattern due to aortic dilatation. […] Either impaired production or enhanced degradation of ECM may promote AAA formation. […] MMPs have been most studied. […] The pathological processes associated with the natural history of aneurysms to dilate and rupture are not well documented in clinical studies. […] Aortic rupture is therefore likely caused by localised elevations in proteolytic enzymes and focal wall weakening. […] In the future it is hoped that research into the mechanism of aortic rupture will integrate biomechanical and basic science research pathways. […] The understanding of mechanisms important in AAA is expanding rapidly within pre-clinical models.

• #1 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Recent studies revealed that intramural thrombus, which is colocalized with the active sites of inflammation and angiogenesis, is closely associated with aortic aneurysm formation. […] Extracellular vesicles (EVs), including plasma membrane-derived microvesicles/ectosomes and apoptotic bodies, and endosome-derived exosomes, are pivotal in regulating cell-to-cell communication.

• #1 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Although the TGF- signaling pathway is the primary mechanism for the synthesis of contractile and ECM proteins, the complexity of this signaling means that the intrinsic role of TGF- in the pathophysiology of aortic aneurysms is unclear. […] Vascular inflammation is the main initiating factor in aortic aneurysms and substantially influences aortic wall remodeling through the death of aortic wall cells, SMC phenotypic switching, and the secretion of proteases. […] Cell death and inflammation are closely associated in pathological environments, including aortic aneurysms. […] Progressive SMC loss is a common pathological feature of aortic aneurysm and dissection. […] Damage to the aortic wall by elastic fiber degradation and deleterious spatial structural remodeling induces coagulation and thrombosis, which results in the maldistribution of oxygen and nutrients from the blood to the aortic wall.

• #1 Mechanisms of Healing in Coiled Intracranial Aneurysms: A Review of the Literature | American Journal of Neuroradiology

  http://www.ajnr.org/content/36/7/1216

  Histopathologic studies have demonstrated that blood clot composed of red blood cells and fibrin is generally present within the first week of aneurysm coiling. […] By the end of the first week following coil embolization, fibroblasts and macrophages begin to invade the clot and foreign body giant cells begin to proliferate about the coils. […] One-to-two weeks following coil embolization, coils within the dome begin to be covered with fibrin. Inflammatory cell, macrophage, and fibroblast invasion occurs in most patients. […] At the site of the aneurysm neck, a thin fibrin membrane forms. […] Two weeks to 1 month following coil embolization, coils in the aneurysm dome are generally covered by a thin layer of fibrin. Fibroblast invasion of the clot in the dome is most vigorous at this phase.

• #1 Underlying mechanism of hemodynamics and intracranial aneurysm | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-021-00260-2

  The mechanical force of blood flow on the tube wall mainly include the stretch of endothelial cells, the impulse force on the tube wall, and the tangential force between the blood flow and the tube wall. […] Under the continuous abnormal blood flow stimulation, the function of the endothelial cells is disordered and becomes the initiating factor of IA development. […] Hypertension, smoking and drinking, environmental factors, and genetic factors are all reported to be risk factors of intracranial aneurysm. […] Many studies evidenced that abnormal hemodynamics is closely related to the occurrence and development of intracranial aneurysms. […] The Willis circle was the most frequent place of IAs development owing to its special anatomy structure, which is reported to be closely related to irregular hemodynamic stimulation.

• #1 Intracranial aneurysm – Wikipedia

  https://en.wikipedia.org/wiki/Intracranial_aneurysm

  An intracranial aneurysm, also known as a cerebral aneurysm, is a cerebrovascular disorder characterized by a localized dilation or ballooning of a blood vessel in the brain due to a weakness in the vessel wall. […] The risk of rupture varies with the size and location of the aneurysm, with those in the posterior circulation being more prone to rupture. […] Saccular aneurysms are the most common type and can result from various risk factors, including genetic conditions, hypertension, smoking, and drug abuse. […] Aneurysm means an outpouching of a blood vessel wall that is filled with blood. Aneurysms occur at a point of weakness in the vessel wall. This can be because of acquired disease or hereditary factors. The repeated trauma of blood flow against the vessel wall presses against the point of weakness and causes the aneurysm to enlarge.

• #1 Intracranial aneurysm – Wikipedia

  https://en.wikipedia.org/wiki/Intracranial_aneurysm

  Both high and low wall shear stress of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall). […] Damage to structural integrity of the arterial wall by shear stress causes an inflammatory response with the recruitment of T cells, macrophages, and mast cells. […] This causes the fibrosis of the arterial wall, with reduction of number of smooth muscle cells, abnormal collagen synthesis, resulting in a thinning of the arterial wall and the formation of aneurysm and rupture. […] Generally, aneurysms larger than 7 mm in diameter should be treated because they are prone for rupture. […] Saccular aneurysms tend to have a lack of tunica media and elastic lamina around their dilated locations (congenital), with a wall of sac made up of thickened hyalinized intima and adventitia.

• #1 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/fusiform-aneurysms-a-review-from-its-pathogenesis-to-treatment-options/

  Fusiform aneurysms are nonsaccular dilatations that involve the vessel wall for a variable distance and it can present different formation process. […] Fusiform aneurysms have different underlying pathologies, hemodynamics, anatomical distributions, natural histories, and treatments compared to the saccular variety. The two principal causes for this type of aneurysm are dissection and atherosclerosis; disorders of collagen and elastin metabolism, by infections, very rarely by neoplastic invasion of the arterial wall and also iatrogenesis are other origins for this vasculopathy. […] An essential feature of the intracranial fusiform aneurysms is the communication between both lumens (the true lumen and the pseudolumen) through a disrupted portion of the internal elastic lamina in most of the cases. A possibility for its evolution is the disruption advance to the adventitia, rupturing the aneurysm and causing a subarachnoid hemorrhage (SAH), or it can be contained by the media layer, which will result in ischemia or stenosis of the artery caused by the enlargement of an aneurysm toward the artery lumen.

• #1 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/fusiform-aneurysms-a-review-from-its-pathogenesis-to-treatment-options/

  A propose for atherosclerotic fusiform aneurysms pathogenesis and evolution is that the initial event in the formation of the aneurysm is a lipid deposition in and beneath the intima. This disrupts the internal elastic membrane (IEM) and infiltrates the muscular wall. Intramural hemorrhage and rupture of the atheroma lead to transmural extension of the thrombus and thicken the intima to create the fusiform shape of an aneurysm. […] The rupture into the vessel lumen of an intramural thrombus can cause a distal embolization. However, the further expansion of the intramural clot will lead to vessel occlusion. […] The principal mechanism to form a fusiform aneurysm is the dissection of the internal wall vessel, what communicates the true lumen and the pseudolumen through a disrupted portion (entry point) of the internal elastic lamina. This leads to dissection with intramural hemorrhage between the intima and media producing focal narrowing of vessel.

• #1 Neoplastic and infectious aneurysms | MedLink Neurology

  https://www.medlink.com/articles/neoplastic-and-infectious-aneurysms

  Infectious aneurysms most often occur in the setting of bacterial sepsis, often bacterial endocarditis, with typical organisms including Staphylococcus and Streptococcus species. Viridans Streptococci is the most common organism, found in 25% to 40% of cases. Less often, infectious aneurysms are truly mycotic, due to fungal species, including Aspergillosis and Candida species. Frequently, the causative organism remains unidentified. Interestingly, a viral cause of infectious aneurysms has been recognized, with reports of aneurysms related to Varicella-zoster virus and a handful of case reports of arteriopathy and aneurysm formation in children and adults with HIV infection. […] Infectious aneurysms occur in infective endocarditis either as the result of embolization of septic material into the vasa vasorum of affected vessels or directly to the lumen, leading to arteritis and sometimes to peri-arterial abscess formation. At times, there can also be invasion of the arterial wall from external infections in meningitis, cavernous thrombophlebitis, osteomyelitis, or chronic sinus infections. The resultant weakening of the vessel wall, under the strain of pulsatile flow, can lead to rapidly progressive aneurysm formation and growth.

• #1 Aneurysm – Wikipedia

  https://en.wikipedia.org/wiki/Aneurysm

  A minority of aneurysms are caused by copper deficiency, which results in a decreased activity of the lysyl oxidase enzyme, affecting elastin, a key component in vessel walls. […] Aneurysmal blood vessels are prone to rupture under normal blood pressure and flow due to the special mechanical properties that make them weaker. […] Blood vessels with aneurysms, on the other hand, are under the influence of an S-shaped stress-strain curve. […] The differences in the mechanical properties of the aneurysmal blood vessels and the healthy blood vessels stem from the compositional differences of the vessels. […] It was also found that the ultimate tensile strength, or the strength to withstand rupture, of aneurysmal vessel wall is 50% lower than that of normal aortas. […] Due to the change in composition of the arterial wall, aneurysms overall have much lower strength to resist rupture. Predicting the risk of rupture is difficult due to the regional anisotropy the hardened blood vessels exhibit, meaning that the stress and strength values vary depending on the region and the direction of the vessel they are measured along.

• #1 Cerebral Aneurysm: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1161518-overview

  The development of cerebral aneurysms remains a controversial topic. A multifactorial etiology is most likely, reflecting the interaction of environmental factors, such as atherosclerosis or hypertension, and a congenital predisposition associated with various vascular abnormalities. […] Environmental stressors, such as hypertension, have been associated with the presence of multiple aneurysms. […] Dolichoectatic aneurysms of proximal vessels most likely have an arteriosclerotic etiology. […] Infectious aneurysms typically are situated in distal branches of the middle cerebral artery (MCA; 7580% of cases), reflecting the embolic origin of these lesions. […] Traumatic aneurysms may be located in peripheral cortical branches secondary to contact with the falcine edge or skull fractures associated with penetrating or closed head injury.

• #1 Understanding the pathogenesis of abdominal aortic aneurysms – PubMed

  https://pubmed.ncbi.nlm.nih.gov/26308600/

  An aortic aneurysm is a dilatation in which the aortic diameter is 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50-80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation and oxidative stress. […] Several biological processes and risk factors have been identified that contribute to AAA pathogenesis. Genes in the biological pathways have been used in candidate gene studies.

• #1 Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

  https://www.mdpi.com/2073-4409/13/3/274

  The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. […] It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes. […] The initiation and development of AAA often is completely asymptomatic, while the risk of severe consequences is constantly increasing. […] AAA has a complex multifactorial etiology, including inflammation, genetic factors or single nucleotide variants (SNV) of individual genes, as matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). […] The most dangerous complication of AAA is its rupture. […] The development of AAA and TAA differs slightly in pathophysiology.

• #1

  https://journals.lww.com/neur/fulltext/2017/65040/molecular_mechanisms_of_the_intracranial_aneurysms.10.aspx

  Long noncoding ribonucleic acids (RNAs) are important regulators of gene expression. Antisense noncoding RNA in the INK4 locus (ANRIL), which was coded on the Chr9p21.3 loci, participates in the pathogenesis of tumor, coronary artery disease, type 2 diabetes mellitus, and other diseases. A genome-wide association study indicated ANRIL to be a candidate gene that may lead to the development of an intracranial aneurysm (IA) formation. […] Through reviewing the molecular mechanisms responsible for the development of IA and the regulation pathway of ANRIL, this paper presents four possible molecular mechanisms that may be responsible for the influence of ANRIL on the development of IAs, that is, cell cycling, Krppel-like factor 2 (KLF2), caspase recruitment domain family member 8, and retinoid metabolism. ANRIL may become a molecular marker or therapeutic target of IA in the future.

• #1 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  Experimental studies have shown that NF-κB activation increases the expression of these markers, and by blocking NF-κB activation, the expression of these inflammatory markers and MMPs could be reduced. […] NF-κB activation increases the transcription and protein expression of inflammatory markers and MMPs. Higher mRNA expression, protein levels, and concentrations of pro-inflammatory markers in serum and IA walls have been reported in clinical and experimental animal studies. The mRNA and protein expression of these inflammatory markers were lowered by pharmacological treatments and genetic manipulations, which also reduced the incidence of IA formation, growth, and rupture. […] Furthermore, blocking NF-κB expression and activation reduced the expression of pro-inflammatory markers including IL-1β, MCP-1, and VCAM-1.

• #1 The molecular mechanism behind abdominal aneurysms

  https://medicalxpress.com/news/2023-02-molecular-mechanism-abdominal-aneurysms.html

  For the final part of the study, the researchers were able to prevent the abdominal arteries from enlarging in the engineered mice when they blocked an angiotensin receptor using the blood pressure drug losartan. […] „Now that the researchers identified some of the components involved in these aneurysms, they will next need to explore how they interact together,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor.

• #1 Innovation in pathogenesis and management of aortic aneurysm

  https://www.wjgnet.com/2220-315x/abstract/v14/i2/91408.htm

  This manuscript explores diverse pathophysiologic pathways (inflammation, atherosclerosis and immune system), varied treatment methods (pharmacological, radiation and surgical), and associated factors like inflammatory markers [transforming growth factor-, interleukin (IL)-1, tumor necrosis factor-, matrix metalloproteinase-2, IL-6, IL-8]. Genetic disorders linked to aortic aneurysms (AA) include Marfan syndrome, Ehler-Danlos syndrome, Loeys-Dietz syndrome, Cantu syndrome, and JAK-2 mutation. Approaches such as Low laser irradiation, photobiomodulation, UV-B irradiation may impact AA prevention and shrinkage. Medications like Canakinumab, Paricalcitol, peroxisome proliferator-activated receptor- agonist and mesenchymal stem cell transplantation are currently under investigation. Additionally, Different minimally invasive, endovascular surgical methods are highlighted.

• #1 The molecular mechanism behind abdominal aneurysms

  https://medicalxpress.com/news/2023-02-molecular-mechanism-abdominal-aneurysms.html

  The molecular mechanism behind abdominal aneurysms […] In a new study using mice, University of Maryland School of Medicine (UMSOM) researchers were able to tease apart the molecular components involved in abdominal aneurysms to better understand how and why they form. […] „Certain genetic mutations may make someone more likely to have their repair process end up going haywire causing the portion of the artery to swell like a balloon and instead of healing a section of damaged artery,” said study co-author Jackie Zhang, MD, Surgery Resident at UMSOM and researcher in Dr. Strickland’s laboratory. […] To conduct the study, the research team decided to focus on the protein LRP1, since it is involved in thoracic aortic aneurysms. […] Next, using a highly sophisticated comparative protein analysis of normal and diseased tissue, they found that the enlarged blood vessels in the genetically engineered mice had higher levels of proteins involved in the hormonal angiotensin-renin system that regulates blood pressure and blood vessel growth and development.

• #2 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta. […] The pathogenic mechanisms and therapeutic targets for aortic aneurysms have been examined over the past decade; however, there are unknown pathogenic mechanisms involved in cellular heterogeneity and plasticity, the complexity of the transforming growth factor- signaling pathway, inflammation, cell death, intramural neovascularization, and intercellular communication. […] Aortic rupture is not only associated with increasing aneurysm diameters but also results from characteristic changes, which involve the progressive expansion and weakening of the three layers of the aorta: the intima, media, and adventitia. […] Multiple pathological processes, including extracellular matrix (ECM) breakdown, inflammation, phenotype switching of vascular smooth muscle cells (SMCs), oxidative stress, and neovascularization, contribute to this process.

• #2 Etiology and Pathogenesis of Aortic Aneurysm | IntechOpen

  https://www.intechopen.com/chapters/44127

  Aortic aneurysm is a multifactorial disease, with both genetic and environmental risk factors contributing to the underlying pathobiology. […] Although the aortic aneurysm morphological characteristics have been well-recognized, the mechanism which elicits its formation is incompletely understood. However, it is generally accepted that an aneurysm results from an association of genetic predisposition, stresses within the aortic wall, proteolytic degradation of the structural components, and/or inflammation and autoimmune response. […] Histological examination demonstrates that the pathophysiological processes in aortic aneurysm involve all layers of the aortic wall in a variable proportion. […] The degenerative atherosclerotic disease results in hypoxia, as the diffusion of blood from the lumen is prevented by the plaques. The consequence is the onset of aortic wall structural anomalies which may lead to arterial dilatation, in a traditional view.

• #2 Underlying mechanism of hemodynamics and intracranial aneurysm | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-021-00260-2

  In modern society, subarachnoid hemorrhage, mostly caused by intracranial aneurysm rupture, is accompanied by high disability and mortality rate, which has become a major threat to human health. […] In recent years, more and more studies focus on the relationship between hemodynamics and intracranial aneurysm. Under the physiological condition, the mechanical force produced by the stable blood flow in the blood vessels keeps balance with the structure of the blood vessels. When the blood vessels are stimulated by the continuous abnormal blood flow, the functional structure of the blood vessels changes, which becomes the pathophysiological basis of the inflammation and atherosclerosis of the blood vessels and further promotes the occurrence and development of the intracranial aneurysm. […] At present, many studies have confirmed that abnormal hemodynamics, as an initiating factor, is involved in the occurrence and development of IA.

• #2 Neoplastic and infectious aneurysms | MedLink Neurology

  https://www.medlink.com/articles/neoplastic-and-infectious-aneurysms

  Infectious aneurysms most often occur in the setting of bacterial sepsis, often bacterial endocarditis, with typical organisms including Staphylococcus and Streptococcus species. Viridans Streptococci is the most common organism, found in 25% to 40% of cases. Less often, infectious aneurysms are truly mycotic, due to fungal species, including Aspergillosis and Candida species. Frequently, the causative organism remains unidentified. Interestingly, a viral cause of infectious aneurysms has been recognized, with reports of aneurysms related to Varicella-zoster virus and a handful of case reports of arteriopathy and aneurysm formation in children and adults with HIV infection. […] Infectious aneurysms occur in infective endocarditis either as the result of embolization of septic material into the vasa vasorum of affected vessels or directly to the lumen, leading to arteritis and sometimes to peri-arterial abscess formation. At times, there can also be invasion of the arterial wall from external infections in meningitis, cavernous thrombophlebitis, osteomyelitis, or chronic sinus infections. The resultant weakening of the vessel wall, under the strain of pulsatile flow, can lead to rapidly progressive aneurysm formation and growth.

• #2 Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

  https://www.oaepublish.com/articles/2347-8659.154433/

  Intracranial aneurysms are a life-threatening cerebrovascular pathology with a probability of spontaneous rupture. Recent investigation has reinforced inflammation’s role in the pathophysiological process of cerebral aneurysms. The majority of evidence from intensive investigation has implicated a mounting inflammatory response during the aneurysm pathogenesis. Hemodynamic insult is considered to be one of the first steps in activating the cerebral vessel walls’ inflammatory response. Upon the hemodynamic insult, this balance is perturbed, leading to vessel wall weakening. Dilation results, as extracellular matrix is degraded by increased levels of matrix metalloproteinases (MMP) compounded by concomitant apoptotic death of vascular smooth muscle cells (VSMCs). Integral disturbances lead to less organization within the aneurysm wall and fewer distinct layers. Simultaneously, MMP activation has been found to facilitate flow-induced internal elastic lamina (IEL) fragmentation. Vascular smooth muscles cells (VSMCs), mainly found in the media layer, are recognized as major producers of matrix in the vessel wall. Upon endothelial injury, intimal thickening occurs as VSMCs migrate into the intima and proliferate. Phenotypic transformation is seen in these migrated VSMCs as environmental change induces a switch from a contractile phenotype to a synthetic pro-inflammatory matrix remodeling phenotype in these cells. Endothelial cells are also affected by the hemodynamic insult. Experimentally, endothelial cells respond to hemodynamic stress with the up-regulation of the inflammatory mediator, prostaglandin E receptor 2 (EP2), during the formation of cerebral aneurysms. As cerebral vessel walls undergo change during aneurysm development, the formation of new vessels, angiogenesis, also contributes to aneurysmal progression. Angiogenesis indirectly advances the inflammatory process of aneurysm progression by aiding in the delivery of inflammatory cells to vessel walls. Human and animal studies have both shown that inflammatory cells and mediators are involved in IA pathogenesis. A number of these inflammatory cells and mediators are highlighted in this section, with a special focus on the most recent investigation. T cells and macrophage infiltration have been found to be associated with human cerebral aneurysm rupture. The role of the inflammatory mediators, chemokines, has been studied in aneurysm formation. These data indicate that inflammatory cells are being actively recruited to the aneurysm wall as a result of high chemokine levels, further contributing to IA formation and eventual rupture. Intensive investigation has implicated the inflammation in the complex pathophysiological processes that underlie IA development, progression, and rupture.

• #2 The mechanism and therapy of aortic aneurysms | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01325-7

  During the formation of the embryonic vascular system, smooth muscle precursor cells are recruited into the vascular network composed of endothelial cells, which are further influenced by various cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor beta (TGF-), and then differentiate into mature VSMCs. […] The contractile phenotype is essential for the aortic wall and maintains aortic strength. In contrast, in the case of inflammation and injury, VSMCs switch to a synthetic phenotype with a strong proliferation and migration capacity, as well as a higher secretion of fibrosis-related proteins and inflammation-related proteins. […] In AA, a decrease in the number of VSMCs can be observed, which could further lead to a decrease in the ECM and weakening of the aortic wall.

• #2 The mechanism and therapy of aortic aneurysms | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01325-7

  The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] Among the MMP family, MMP-2/9 is the most studied matrix metalloproteinase. High levels of MMP-2/9 expression can be observed in AA tissue. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] Autophagy is a lysosome-mediated process that removes damaged proteins and organelles. […] The immune response plays an important role in the course of AA. […] Immune cells not only secrete inflammatory factors that lead to apoptosis of aortic wall cells and VSMC phenotype switching but also secrete proteases that induce ECM degradation and lead to aortic dilation and rupture.

• #2 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Although the TGF- signaling pathway is the primary mechanism for the synthesis of contractile and ECM proteins, the complexity of this signaling means that the intrinsic role of TGF- in the pathophysiology of aortic aneurysms is unclear. […] Vascular inflammation is the main initiating factor in aortic aneurysms and substantially influences aortic wall remodeling through the death of aortic wall cells, SMC phenotypic switching, and the secretion of proteases. […] Cell death and inflammation are closely associated in pathological environments, including aortic aneurysms. […] Progressive SMC loss is a common pathological feature of aortic aneurysm and dissection. […] Damage to the aortic wall by elastic fiber degradation and deleterious spatial structural remodeling induces coagulation and thrombosis, which results in the maldistribution of oxygen and nutrients from the blood to the aortic wall.

• #2 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  The pathophysiology of IAs is complex. Although many factors play together in the formation, progression, and rupture of IAs, the research hitherto suggests that inflammation heavily contributes to IAs from formation to rupture. The endothelial dysfunction, smooth muscle cells (SMCs) phenotypic switching, infiltration and accumulation of inflammatory cells in the arterial walls, and the expression and release of pro-inflammatory cytokines such as interleukin (IL) -1β, and tumor necrosis factor-alpha (TNF-α), chemokines such as monocyte chemoattractant protein-1 (MCP-1), and IL-8, cell adhesion molecules, namely, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and extracellular matrix remodeling proteinases such as MMPs including MMP-2 and MMP-9 have been implicated in IA formation and rupture. The expression of these pro-inflammatory markers and MMPs is regulated by NF-κB transcription activity.

• #2 Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

  https://www.oaepublish.com/articles/2347-8659.154433

  Intracranial aneurysms are a life-threatening cerebrovascular pathology with a probability of spontaneous rupture. Recent investigation has reinforced inflammation’s role in the pathophysiological process of cerebral aneurysms. The majority of evidence from intensive investigation has implicated a mounting inflammatory response during the aneurysm pathogenesis. Hemodynamic insult is considered to be one of the first steps in activating the cerebral vessel walls inflammatory response. Upon the hemodynamic insult, this balance is perturbed, leading to vessel wall weakening. Dilation results, as extracellular matrix is degraded by increased levels of matrix metalloproteinases (MMP) compounded by concomitant apoptotic death of vascular smooth muscle cells (VSMCs). Initially, the vessel wall is highly organized. Integral disturbances lead to less organization within the aneurysm wall and fewer distinct layers. Simultaneously, MMP activation has been found to facilitate flow-induced internal elastic lamina (IEL) fragmentation. Vascular smooth muscles cells (VSMCs), mainly found in the media layer, are recognized as major producers of matrix in the vessel wall. Upon endothelial injury, intimal thickening occurs as VSMCs migrate into the intima and proliferate. Phenotypic transformation is seen in these migrated VSMCs as environmental change induces a switch from a contractile phenotype to a synthetic pro-inflammatory matrix remodeling phenotype in these cells. Endothelial cells are also affected by the hemodynamic insult. As blood flows, mechanical stimulus has notable effects on the cells of the vascular system. Consequently, IAs develop in vessel regions exposed to high hemodynamic stress such as arterial bifurcations and sharp angles. Experimentally, endothelial cells respond to hemodynamic stress with the up-regulation of the inflammatory mediator, prostaglandin E receptor 2 (EP2), during the formation of cerebral aneurysms. As cerebral vessel walls undergo change during aneurysm development, the formation of new vessels, angiogenesis, also contributes to aneurysmal progression. Angiogenesis indirectly advances the inflammatory process of aneurysm progression by aiding in the delivery of inflammatory cells to vessel walls. Human and animal studies have both shown that inflammatory cells and mediators are involved in IA pathogenesis. A number of these inflammatory cells and mediators are highlighted in this section, with a special focus on the most recent investigation. T cells and macrophage infiltration have been found to be associated with human cerebral aneurysm rupture. The role of the inflammatory mediators, chemokines, has been studied in aneurysm formation. These data indicate that inflammatory cells are being actively recruited to the aneurysm wall as a result of high chemokine levels, further contributing to IA formation and eventual rupture. Intensive investigation has implicated the inflammation in the complex pathophysiological processes that underlie IA development, progression, and rupture.

• #2 Intracranial Aneurysm Development 101: Pathogenesis and Risk Factors

  https://consultqd.clevelandclinic.org/intracranial-aneurysm-development-101-pathogenesis-and-risk-factors

  Evidence mounts that inflammation plays a key role […] Recently, increased focus has been placed on the role of inflammation in causing vascular smooth muscle dysfunction, driving both aneurysm formation and rupture, especially in vulnerable individuals. […] The role of inflammation in aneurysm pathogenesis is an important focus of research. Current evidence points to a complex interplay between endothelial dysfunction, inflammatory responses and flow dynamics that eventually leads to aneurysm rupture. […] Areas of vessel dysfunction or injury attract macrophages, mast cells and T cells, which then contribute to alteration of vascular smooth muscle cells. As macrophages release cytokines and other mediators, matrix metalloproteinases cleave the extracellular matrix, inducing a positive feedback cycle that further promotes migration of inflammatory cells.

• #2 Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

  https://www.mdpi.com/2073-4409/13/3/274

  A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. […] The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. […] The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. […] Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases.

• #2 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  Experimental studies have shown that NF-κB activation increases the expression of these markers, and by blocking NF-κB activation, the expression of these inflammatory markers and MMPs could be reduced. […] NF-κB activation increases the transcription and protein expression of inflammatory markers and MMPs. Higher mRNA expression, protein levels, and concentrations of pro-inflammatory markers in serum and IA walls have been reported in clinical and experimental animal studies. The mRNA and protein expression of these inflammatory markers were lowered by pharmacological treatments and genetic manipulations, which also reduced the incidence of IA formation, growth, and rupture. […] Furthermore, blocking NF-κB expression and activation reduced the expression of pro-inflammatory markers including IL-1β, MCP-1, and VCAM-1.

• #2 Etiology and Pathogenesis of Aortic Aneurysm | IntechOpen

  https://www.intechopen.com/chapters/44127

  The action of proteolytic enzymes, notably matrix metalloproteases and serine proteases, has been associated with the destruction of the extracellular matrix. […] Aortic aneurysm is a multifactorial disease, with both genetic and environmental risk factors contributing in variable degrees to the underlying pathobiology, leading to proteolytic degradation of aortic wall components, stresses within the aortic wall, and variable intervention of inflammation and/or autoimmune response. […] Numerous research data provide valuable mechanistic insight into the genetic, environmental, and mechanistic pathogenesis of aortic aneurysm, reveal diagnostic markers, and identifies new therapeutic targets, such as recently described theranostic approaches.

• #2 Cellular, Molecular and Clinical Aspects of Aortic Aneurysm—Vascular Physiology and Pathophysiology

  https://www.mdpi.com/2073-4409/13/3/274

  Overactive matrix metalloproteinases (MMPs) family proteins play a major role in AAA pathogenesis, especially MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14. […] Another hallmark of AAA is a strong inflammation, engaging immune cells as well as inflammatory pathway activation, like FOS and interleukine-17 (IL-17), interleukin-1β (IL-1β) and nuclear factor κB (NF-κB). […] The interplay of infiltrated inflammatory cells is complex in forming the inflammatory environment during AAA development. […] The action of even one of the factors described above causes a cascade of degradation and a weakening of the aortic wall, weaving a complex network of AAA pathogenesis and development, influencing pathways of molecular factors.

• #2 175 PATHOGENESIS OF ABDOMINAL AORTIC ANEURYSMS: THE ROLE OF METALLOPROTEINASES AND THEIR INHIBITORS | Heart

  https://heart.bmj.com/content/99/suppl_2/A100.2

  An abdominal aortic aneurysm (AAA) represents a complex pathophysiological process of weakening and dilatation of the aortic wall, which is associated with atherosclerosis, a chronic inflammatory response and hemodynamic alterations. […] Degradation of the extracellular matrix by the matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs), as well as the production of reactive oxygen species, have fundamental roles in the development of AAA. […] The exact pathogenetic mechanisms remain incompletely elucidated. […] The inflammatory process associated with turbulent intraluminal flow most likely causes endothelial dysfunction that creates a milieu favorable to the release of MMPs. […] The MMPs cause massive destruction of elastin fibers which significantly remodels the arterial wall, resulting in dilatation and AAA formation.

• #2

  https://apcz.umk.pl/JEHS/article/view/41015

  Abdominal aortic aneurysms (AAA) affect 2.4% of the population, with men being five times more likely to be affected than women. The development of AAA is linked to changes in the elastin and vascular wall collagen. The enzymes that damage the cell wall are called metalloproteinases. AAA forms as a result of damage to elastic fibres and the loss of the property of reversible deformation of the aortic wall. The degradation of elastin and other stem proteins in the aortic wall is caused by metalloproteinases and serine proteases, accompanied by cysteine proteases and asparagine proteases. Increased calprotectin levels are observed in AAA patients in comparison to patients with a healthy aorta. A significant role in the pathogenesis of AAA and its rupture is played by inflammatory response cells; proteases of the tissue plasma coagulation and fibrinolysis.

• #2 175 PATHOGENESIS OF ABDOMINAL AORTIC ANEURYSMS: THE ROLE OF METALLOPROTEINASES AND THEIR INHIBITORS | Heart

  https://heart.bmj.com/content/99/suppl_2/A100.2

  Reactive oxygen species play a role in the development of aneurysms. […] Increasing the levels of TIMPs, proportional to the increased levels of ROS, was not sufficient to block the formation of AAA. […] Further studies are being conducted to elucidate the role of inflammatory cells and turbulent blood flow in the pathogenesis of AAAs in this experimental model.

• #2 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Recent studies revealed that intramural thrombus, which is colocalized with the active sites of inflammation and angiogenesis, is closely associated with aortic aneurysm formation. […] Extracellular vesicles (EVs), including plasma membrane-derived microvesicles/ectosomes and apoptotic bodies, and endosome-derived exosomes, are pivotal in regulating cell-to-cell communication.

• #2 Mechanisms of Healing in Coiled Intracranial Aneurysms: A Review of the Literature | American Journal of Neuroradiology

  http://www.ajnr.org/content/36/7/1216

  In addition, there is continued invasion of the aneurysm dome by inflammatory cells, macrophages, and fibrocytes. […] Three-to-twelve months following embolization, there is increased vascularized connective tissue within the aneurysm dome and about the coils. […] Gene and protein studies have demonstrated that factors such as MMPs and osteopontin may play an integral role in the aneurysm-healing process. Findings from histopathologic and molecular studies have been applied to develop treatment methods aimed at improving the aneurysm-healing process.

• #2 Underlying mechanism of hemodynamics and intracranial aneurysm | Chinese Neurosurgical Journal | Full Text

  https://cnjournal.biomedcentral.com/articles/10.1186/s41016-021-00260-2

  To further elucidate the causes of IA location in brain artery, many researches focused on the correlation between IA location and WSS level. […] In the further development of aneurysms, researchers believe that longitudinal blood flow impinging on the vessel wall is an important risk factor in aneurysm growth, and continuous blood flow further destroys the structure of the vascular wall. […] The low WSS condition formed by blood flow is similar to the environment forming atherosclerotic plaque, which further explains that atherosclerotic lesions are often found in the anatomy of IA. […] The chronic inflammation further provides an ideal environment for the formation of atherosclerotic plaque. The atherosclerosis and inflammation jointly promote IA occurrence and development.

• #2 Aneurysm | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/aneurysm

  An aneurysm is an abnormal swelling or bulge in the wall of a blood vessel, such as an artery. […] Aneurysms can occur anywhere throughout the circulatory system, but most commonly develop along the aorta (the bodys main artery that runs the length of the trunk) and in blood vessels of the brain. […] Aneurysms are potentially fatal if they rupture. […] It begins as a weak spot in the blood vessel wall, which balloons out of shape over time by the force of the pumping blood. […] Usually, aneurysms develop at the point where a blood vessel branches, because the fork is structurally more vulnerable. […] Some of the causes of aneurysms include: a weakness in the blood vessel wall that is present from birth (congenital aneurysm), high blood pressure (hypertension) over many years resulting in damage and weakening of blood vessels, fatty plaques (atherosclerosis) resulting in a weakness of the blood vessel wall, inherited diseases that may result in weaker than normal blood vessel walls, trauma, such as a crush injury to the chest, the sexually transmitted infection (STI) syphilis, if untreated, targeting the aorta and weakening its walls, polycystic kidney disease increasing the risk of cerebral aneurysm, very occasionally, an infection targeting and weakening a section of blood vessel.

• #2 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/fusiform-aneurysms-a-review-from-its-pathogenesis-to-treatment-options/

  Fusiform aneurysms are nonsaccular dilatations that involve the vessel wall for a variable distance and it can present different formation process. […] Fusiform aneurysms have different underlying pathologies, hemodynamics, anatomical distributions, natural histories, and treatments compared to the saccular variety. The two principal causes for this type of aneurysm are dissection and atherosclerosis; disorders of collagen and elastin metabolism, by infections, very rarely by neoplastic invasion of the arterial wall and also iatrogenesis are other origins for this vasculopathy. […] An essential feature of the intracranial fusiform aneurysms is the communication between both lumens (the true lumen and the pseudolumen) through a disrupted portion of the internal elastic lamina in most of the cases. A possibility for its evolution is the disruption advance to the adventitia, rupturing the aneurysm and causing a subarachnoid hemorrhage (SAH), or it can be contained by the media layer, which will result in ischemia or stenosis of the artery caused by the enlargement of an aneurysm toward the artery lumen.

• #2 Intracranial aneurysm – Wikipedia

  https://en.wikipedia.org/wiki/Intracranial_aneurysm

  Both high and low wall shear stress of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall). […] Damage to structural integrity of the arterial wall by shear stress causes an inflammatory response with the recruitment of T cells, macrophages, and mast cells. […] This causes the fibrosis of the arterial wall, with reduction of number of smooth muscle cells, abnormal collagen synthesis, resulting in a thinning of the arterial wall and the formation of aneurysm and rupture. […] Generally, aneurysms larger than 7 mm in diameter should be treated because they are prone for rupture. […] Saccular aneurysms tend to have a lack of tunica media and elastic lamina around their dilated locations (congenital), with a wall of sac made up of thickened hyalinized intima and adventitia.

• #2 < ?php wp_title( '|', true, 'right' ); ?>

  https://surgicalneurologyint.com/surgicalint-articles/fusiform-aneurysms-a-review-from-its-pathogenesis-to-treatment-options/

  A propose for atherosclerotic fusiform aneurysms pathogenesis and evolution is that the initial event in the formation of the aneurysm is a lipid deposition in and beneath the intima. This disrupts the internal elastic membrane (IEM) and infiltrates the muscular wall. Intramural hemorrhage and rupture of the atheroma lead to transmural extension of the thrombus and thicken the intima to create the fusiform shape of an aneurysm. […] The rupture into the vessel lumen of an intramural thrombus can cause a distal embolization. However, the further expansion of the intramural clot will lead to vessel occlusion. […] The principal mechanism to form a fusiform aneurysm is the dissection of the internal wall vessel, what communicates the true lumen and the pseudolumen through a disrupted portion (entry point) of the internal elastic lamina. This leads to dissection with intramural hemorrhage between the intima and media producing focal narrowing of vessel.

• #2 Intracranial Fusiform Aneurysms: It’s Pathogenesis, Clinical Characteristics and Managements.

  https://www.jkns.or.kr/journal/view.php?number=1519

  Intracranial Fusiform Aneurysms: It’s Pathogenesis, Clinical Characteristics and Managements. […] The objective of this study is to investigate clinical characteristics, management methods and possible causes of intracranial fusiform aneurysm. […] The possible causes of fusiform aneurysms were regard as dissection in 16, atherosclerosis in 4 and collagen disease or uncertain in 2 cases. […] Although the dissection or injury of internal elastic lamina of the cerebral vessel is proposed as the underlying cause for most of fusiform aneurysm, more study about pathogenesis of these lesions is required.

• #2 Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms in: Journal of Neurosurgery Volume 94 Issue 5 (2001) Journals

  https://thejns.org/view/journals/j-neurosurg/94/5/article-p712.xml

  The goal of this study was to investigate the pathological mechanism and precise three-dimensional (3D) structure of cerebral dissecting aneurysms in association with their clinical course. […] The primary mechanism by which a cerebral dissecting aneurysm is created is by the sudden disruption of the IEL. The plane of dissection extends through the media. The majority of aneurysms have one entrance into the pseudolumen (entry-only type). This type is associated with an unstable clinical course. Some cerebral dissecting aneurysms have both an entrance and exit (entry-exit type). This type of aneurysm occasionally contains a constant flow of blood through the pseudolumen and is clinically more stable than entry-only aneurysms.

• #2 Aneurysm | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/aneurysm

  The cause sometimes remains unknown. […] Depending on the location of the aneurysm, some of the possible complications of an untreated aneurysm include: blood clots within the aneurysm, compression of nearby nerves, if the aneurysm is large enough, blood leaking out of the intact aneurysm into the walls of the artery (dissecting aneurysm), impaired blood circulation beyond the point of the aneurysm, haemorrhage in the layers of tissue surrounding the brain (subarachnoid haemorrhage), water on the brain (hydrocephalus), stroke, epilepsy, paralysis, congestive heart failure, heart attack, kidney failure, sudden death. […] Treatment for an aneurysm depends on its location and severity, but may include: Cerebral aneurysm is repaired either by coils or stent insertion, or by surgery where the aneurysm has been clipped.

• #2

  https://link.springer.com/article/10.1007/BF02000279

  The incidence of abdominal aortic aneurysm has recently increased. […] Abdominal aortic aneurysm is a multi-factorial disease associated with aortic aging and atheroma. […] Particular hemodynamic conditions in the infrarenal abdominal aorta seem to enhance the development of aneurysm at this level. […] While certain constitutional anomalies of the extracellular matrix of proteins seem to enhance the development of abdominal aortic aneurysm, protease activity of as yet undetermined origin also seems to play a prominent role. […] Family cases of abdominal aortic aneurysms have been reported but the mechanisms responsible remain to be determined. […] Several genetic markers have been suggested. […] The most reliable marker of aortic aneurysm is arteriomegaly. […] Cellular, enzymatic and genetic factors in the pathogenesis of abdominal aortic aneurysms.

• #2

  https://journals.lww.com/neur/fulltext/2017/65040/molecular_mechanisms_of_the_intracranial_aneurysms.10.aspx

  The four possible molecular mechanisms of ANRIL on the development of intracranial aneurysms include its influence on cell cycling, Krppel-like factor 2 (KLF2), caspase recruitment domain family member 8, and retinoid metabolism. […] With the advent of genome-wide association study (GWAS), it is frequently reported that the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), has a significant association with an IA. However, the detailed mechanism has not been clarified. […] The linkage between ANRIL and IAs has been proved in a series of GWAS. […] The combined effects of the three loci showed a more than threefold increase than the effect of a single locus. […] Studies show that ANRIL is the genetic susceptible locus for coronary heart disease, abdominal aortic aneurysm (AAA), and ischemic stroke.

• #2 The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

  https://www.mdpi.com/1422-0067/24/18/14218

  Taken together, these studies suggest that the pharmacological drugs, which can block NF-κB activation and can suppress the consequent expression and release of cytokines, chemokines, cell adhesion molecules, and MMPs in macrophages and SMCs, can be suitable candidates that might reduce IA formation and rupture.

• #2 2023 News – The Molecular Mechanism Behind Abdominal Aneurysms | University of Maryland School of Medicine

  https://www.medschool.umaryland.edu/news/2023/The-Molecular-Mechanism-Behind-Abdominal-Aneurysms.html

  In a new study using mice, University of Maryland School of Medicine (UMSOM) researchers were able to tease apart the molecular components involved in abdominal aneurysms to better understand how and why they form. […] Certain genetic mutations may make someone more likely to have their repair process end up going haywire causing the portion of the artery to swell like a balloon and instead of healing a section of damaged artery, said study co-author Jackie Zhang, MD. […] To conduct the study, the research team decided to focus on the protein LRP1, since it is involved in thoracic aortic aneurysms. […] Now that the researchers identified some of the components involved in these aneurysms, they will next need to explore how they interact together, said UMSOM Dean Mark T. Gladwin, MD.

• #2 Aortic aneurysms: current pathogenesis and therapeutic targets | Experimental & Molecular Medicine

  https://www.nature.com/articles/s12276-023-01130-w

  Although the pathological mechanisms of aortic aneurysms have been defined, there are no effective drugs to treat aortic aneurysm growth or rupture. […] The loss of structural integrity due to vascular SMC dysfunction, including apoptosis and ECM degradation, leads to weakness and dilatation of the aortic wall, which are hallmarks of aortic aneurysm. […] An imbalance in reparative/ECM production and inflammatory/ECM degradation in SMCs that underwent phenotypic switching and are known as synthetic SMCs in response to constant pathological stimuli damages the aortic wall, leading to dilatation and rupture in aortic aneurysms. […] The components of the transforming growth factor- (TGF-) signaling pathway, including receptors and SMAD proteins, are fundamental for synthesizing SMC contractile proteins, ECM proteins, elastin, and collagen.

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