Materiały źródłowe

• #1 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

• #2 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. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. […] The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. […] In the past 30 years, considerable progress has been made in the research of the pathogenesis of aneurysms under multidisciplinary efforts involving molecular and cellular biology and solid and fluid mechanics.

• #3 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. […] Numerous research data provide valuable mechanistic insight into the genetic, environmental, and mechanistic pathogenesis of aortic aneurysm, reveal diagnostic markers, and identify new therapeutic targets, such as recently described theranostic approaches.

• #4 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.

• #5 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.

• #6 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. […] Numerous research data provide valuable mechanistic insight into the genetic, environmental, and mechanistic pathogenesis of aortic aneurysm, reveal diagnostic markers, and identify new therapeutic targets, such as recently described theranostic approaches.

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

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

  Furthermore, these biological mechanisms are thought to initiate the degradation of elastic fibers and alterations in collagen composition, ultimately compromising the structural integrity and reducing the flexibility of the aortic wall. […] 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.

• #8 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. […] Disruption of elastin has been particularly implicated in AAA development and progression, while degradation of collagen is thought to be more important in AAA rupture. […] 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.

• #9 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.

• #10 Pathology Outlines – Aortic aneurysms

  https://www.pathologyoutlines.com/topic/heartcoronaryarteritis.html

  Progressive, irreversible, localized dilatation of the aortic wall (involving all 3 layers) exceeding the expected aortic diameter by > 1.5 fold […] Majority of cases are asymptomatic until rupture, which is fatal (> 80% estimated mortality) (J Vasc Surg 2018;68:612) […] Aneurysm size and growth rate are the best predictors of risk of rupture (Gen Thorac Cardiovasc Surg 2019;67:1) […] Characteristic histologic findings include disruption of elastic lamellae, loss of smooth muscle cells, inflammation infiltration, increased proteolysis of extracellular matrix (Cardiovasc Pathol 2016;25:247) […] Medial degeneration, led by 3 interconnected processes (Cardiovasc Pathol 2016;25:432) […] Excessive extracellular matrix (ECM) degradation […] Disruption of elastin and collagen homeostasis

• #11 Pathophysiology of abdominal aortic aneurysm: biomarkers and novel therapeutic targets | Clínica e Investigación en Arteriosclerosis (English Edition)

  https://www.elsevier.es/en-revista-clinica-e-investigacion-arteriosclerosis-english-415-articulo-pathophysiology-abdominal-aortic-aneurysm-biomarkers-S2529912319300385

  Abdominal aortic aneurysm (AAA) is a vascular pathology which consists of a localised and permanent dilation of the aorta due to a weakening of the vascular wall. Generally, it manifests in the infrarenal portion of the aorta, a region which is subjected to significant haemodynamic forces. An aneurysm is defined as a dilation greater than 50% of the normal diameter of the vessel in adjacent areas, meaning that, in the abdominal aorta, a diameter greater than or equal to 3cm is considered pathological. The natural development of an AAA supposes a progressive dilation, characterised by the proteolysis of the structural components of the vascular wall, the loss of vascular smooth muscle cells (VSMCs) and a chronic immunoinflammatory response. Vascular dilation in an AAA is progressive, but not linear, with alternating phases of acceleration and periods of stability, making monitoring of the patient difficult, and, therefore, worsening the prognosis of the disease. Vascular dilation can culminate in the rupture of the vascular wall, the most severe complication of this disease associated with 80% mortality.1,2 Recent research suggests that an AAA is a local display of a systemic vascular disease, with involvement of the patient’s entire vascular tree existing in most cases. In addition, in patients with an AAA, a significant link has been demonstrated with coronary heart disease and with peripheral arterial disease. In this review, the main aspects related to the epidemiology, diagnosis and therapeutic management, risk factors and difficulties in having good biomarkers for this disease are gathered.

• #12 Innovation in pathogenesis and management of aortic aneurysm

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

  The ECM is a dynamic structural component of the aortic wall that plays a crucial role in AAA formation, notably through modification by MMPs. Various MMPs have different ECM collagen substrates. A set of processes involving individual risk factors, molecular mechanisms, and triggers leads to degradation of the ECM in the tunica intima and media, all of which contribute to inflammatory infiltration. […] Loss of vascular smooth muscle cells (vSMCs), predominant in the middle aortic wall layer, causes weakening and contributes to AAA formation and progression. This condition occurs due to inflammatory cell infiltration that induces apoptosis, mechanical wall stress, and detachment of the ECM.

• #13 Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development

  https://www.mdpi.com/2075-4418/13/2/253

  Thoracic aorta aneurysm is most frequently associated with MFS, but all these syndromes can be used in order to understand the pathogenesis of aortic wall degeneration in aortic aneurysms. […] The aortic extracellular matrix has high concentrations of elastin and collagen and has an important role in organizing the abdominal aortic wall. […] These mechanisms are considered to have a major role in aortic dilatation and subsequent rupture. […] The similarity between AAA and TAA (thoracic aortic aneurysms) consists of a diminishment in elastin, collagen, and glycosaminoglycans compared to the structure of the normal aortic wall. […] The morpho pathological anomalies found when analyzing the aortic wall sample obtained through surgery consist of infiltration with leukocytes, extracellular matrix degradation, and disfunctions of smooth muscle cells.

• #14 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. […] The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. […] Aortic aneurysm development and progression have been directly associated with a deficiency of elastin as well as a loss of collagen type 1. […] The elastin-to-collagen ratio is also significantly higher in aneurysmal abdominal aortas compared to healthy abdominal aortas. […] While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.

• #15 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. […] The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. […] Aortic aneurysm development and progression have been directly associated with a deficiency of elastin as well as a loss of collagen type 1. […] The elastin-to-collagen ratio is also significantly higher in aneurysmal abdominal aortas compared to healthy abdominal aortas. […] While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.

• #16

  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. Plasminogen activator and plasmin accelerate the degradation of the aortic wall.

• #17 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. […] Disruption of elastin has been particularly implicated in AAA development and progression, while degradation of collagen is thought to be more important in AAA rupture. […] 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.

• #18 175 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 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.

• #19 Pathogenesis of Abdominal Aortic Aneurysms – Clinical Tree

  https://clinicalpub.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Abdominal aortic aneurysm (AAA) development is a complex, multifactorial process involving destructive remodeling of aortic wall connective tissue. Four interrelated factors involved in this process include: (1) chronic inflammation associated with neovascularization and increased proinflammatory cytokine production, (2) increased and dysregulated production of matrix-degrading proteinases, (3) destruction of structural matrix proteins, and (4) decreased medial smooth muscle cell (SMC) presence, resulting in impaired connective tissue repair. […] This understanding has developed from a characterization of human AAA tissue, as well as the use of different animal models that replicate human disease. […] MMPs play an integral role in the inflammatory processes associated with AAA formation.

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

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

  In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] In AA, the role of TGF- is still controversial. […] The immune response plays an important role in the course of AA. […] The differentiation of TH1 cells depends on the stimulation of IL-12, which in turn secretes interferon- (IFN-) to promote the activation and recruitment of macrophages. […] IL-6 is an important inflammatory factor involved in many proinflammatory processes in the body. […] IL-1 plays a central role in mediating the inflammatory response and mediates the activation of secondary inflammatory factors such as IL-6. […] Cytokines play an important role in AA. […] The NLRP3 inflammasome consists of the sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and the effector enzyme pro-caspase-1.

• #21 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.

• #22 Pathogenesis of Abdominal Aortic Aneurysms | Thoracic Key

  https://thoracickey.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Abdominal aortic aneurysm (AAA) development is a complex, multifactorial process involving destructive remodeling of aortic wall connective tissue. Four interrelated factors involved in this process include: (1) chronic inflammation associated with neovascularization and increased proinflammatory cytokine production, (2) increased and dysregulated production of matrix-degrading proteinases, (3) destruction of structural matrix proteins, and (4) decreased medial smooth muscle cell (SMC) presence, resulting in impaired connective tissue repair. […] This understanding has developed from a characterization of human AAA tissue, as well as the use of different animal models that replicate human disease. […] MMPs play an integral role in the inflammatory processes associated with AAA formation. The MMPs include at least 15 structurally related proteinases that are a subfamily of the metazincin superfamily of proteinases. Substrates of the MMPs include elastin, noncollagenase extracellular matrix (ECM) proteins, including fibronectin and laminin, and nonstructural components. […] Numerous MMPS including 1, 2, 3, 8, 9, 10, 12, and 13 play roles in AAA formation. MMPs 1, 8, and 13 are capable of initiating the degradation of fibrillar collagen, and MMPs 2 and 9, both overexpressed in human and experimental AAAs, have both elastolytic and collagenolytic properties.

• #23 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.

• #24 Pathogenesis of Abdominal Aortic Aneurysms – Clinical Tree

  https://clinicalpub.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Numerous MMPS including 1, 2, 3, 8, 9, 10, 12, and 13 play roles in AAA formation. […] MMPs 1, 8, and 13 are capable of initiating the degradation of fibrillar collagen, and MMPs 2 and 9, both overexpressed in human and experimental AAAs, have both elastolytic and collagenolytic properties. […] The presence of constitutive MMP2 in smaller AAAs suggests a possible role for MMP2 in early aneurysm formation. […] MMP9 is not typically produced in normal aorta, but it is present in atherosclerotic plaques, suggesting a possible role in plaque rupture. […] MMP9 expression is increased in the serum and aortic tissue of AAA patients compared to that of patients with aortoiliac occlusive disease. […] There is a correlation between MMP9 expression and AAA size, and it appears to play a role in AAA expansion and ultimate rupture.

• #25 Pathogenesis of Abdominal Aortic Aneurysms – Clinical Tree

  https://clinicalpub.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Numerous MMPS including 1, 2, 3, 8, 9, 10, 12, and 13 play roles in AAA formation. […] MMPs 1, 8, and 13 are capable of initiating the degradation of fibrillar collagen, and MMPs 2 and 9, both overexpressed in human and experimental AAAs, have both elastolytic and collagenolytic properties. […] The presence of constitutive MMP2 in smaller AAAs suggests a possible role for MMP2 in early aneurysm formation. […] MMP9 is not typically produced in normal aorta, but it is present in atherosclerotic plaques, suggesting a possible role in plaque rupture. […] MMP9 expression is increased in the serum and aortic tissue of AAA patients compared to that of patients with aortoiliac occlusive disease. […] There is a correlation between MMP9 expression and AAA size, and it appears to play a role in AAA expansion and ultimate rupture.

• #26 Pathogenesis of Abdominal Aortic Aneurysms – Clinical Tree

  https://clinicalpub.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Numerous MMPS including 1, 2, 3, 8, 9, 10, 12, and 13 play roles in AAA formation. […] MMPs 1, 8, and 13 are capable of initiating the degradation of fibrillar collagen, and MMPs 2 and 9, both overexpressed in human and experimental AAAs, have both elastolytic and collagenolytic properties. […] The presence of constitutive MMP2 in smaller AAAs suggests a possible role for MMP2 in early aneurysm formation. […] MMP9 is not typically produced in normal aorta, but it is present in atherosclerotic plaques, suggesting a possible role in plaque rupture. […] MMP9 expression is increased in the serum and aortic tissue of AAA patients compared to that of patients with aortoiliac occlusive disease. […] There is a correlation between MMP9 expression and AAA size, and it appears to play a role in AAA expansion and ultimate rupture.

• #27 Pathogenesis of Abdominal Aortic Aneurysms – Clinical Tree

  https://clinicalpub.com/pathogenesis-of-abdominal-aortic-aneurysms/

  Furthermore, endovascular exclusion of AAAs results in decreased MMP9 levels. […] The expression of MMP12 is also increased in AAA tissue, and an association with aortic media elastin has been identified. […] The cystine proteases, including cathepsins K, L, and S, also play roles in AAA formation. […] The expression of all cathepsins is increased in human AAA tissue compared to normal aortic tissue. […] Cathepsin K is the most potent elastolytic enzyme. […] The constitutive expression of cystatin C is significantly decreased in AAA patients. […] Furthermore, immunohistochemical analyses of human AAA tissue have demonstrated increases in cathepsin S expression and decreases in cystatin C expression compared to that in normal AAA tissue.

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

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

  In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] In AA, the role of TGF- is still controversial. […] The immune response plays an important role in the course of AA. […] The differentiation of TH1 cells depends on the stimulation of IL-12, which in turn secretes interferon- (IFN-) to promote the activation and recruitment of macrophages. […] IL-6 is an important inflammatory factor involved in many proinflammatory processes in the body. […] IL-1 plays a central role in mediating the inflammatory response and mediates the activation of secondary inflammatory factors such as IL-6. […] Cytokines play an important role in AA. […] The NLRP3 inflammasome consists of the sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and the effector enzyme pro-caspase-1.

• #29 175 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 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.

• #30 Innovation in pathogenesis and management of aortic aneurysm

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

  The ECM is a dynamic structural component of the aortic wall that plays a crucial role in AAA formation, notably through modification by MMPs. Various MMPs have different ECM collagen substrates. A set of processes involving individual risk factors, molecular mechanisms, and triggers leads to degradation of the ECM in the tunica intima and media, all of which contribute to inflammatory infiltration. […] Loss of vascular smooth muscle cells (vSMCs), predominant in the middle aortic wall layer, causes weakening and contributes to AAA formation and progression. This condition occurs due to inflammatory cell infiltration that induces apoptosis, mechanical wall stress, and detachment of the ECM.

• #31 Pathology Outlines – Aortic aneurysms

  https://www.pathologyoutlines.com/topic/heartcoronaryarteritis.html

  Increase in matrix metalloproteinase activity leading to extensive proteolysis […] Inflammation […] Inflammatory cell infiltration and activation of proteases (Circ Res 2019;124:607) […] Smooth muscle cell (SMC) apoptosis […] Significant loss or disorganization of smooth muscle cells within the intima media […] Degradation of the aortic wall → weakening of the aortic wall → dilation of the aorta → increased aortic wall stress → further wall weakening and risk of rupture […] Hypertension and atherosclerosis accelerate medial degeneration […] Significant loss of smooth muscle cells is a characteristic process of medial degeneration in aortic aneurysm.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

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

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

  Furthermore, these biological mechanisms are thought to initiate the degradation of elastic fibers and alterations in collagen composition, ultimately compromising the structural integrity and reducing the flexibility of the aortic wall. […] 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.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

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

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

  Furthermore, these biological mechanisms are thought to initiate the degradation of elastic fibers and alterations in collagen composition, ultimately compromising the structural integrity and reducing the flexibility of the aortic wall. […] 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.

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

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

  In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] In AA, the role of TGF- is still controversial. […] The immune response plays an important role in the course of AA. […] The differentiation of TH1 cells depends on the stimulation of IL-12, which in turn secretes interferon- (IFN-) to promote the activation and recruitment of macrophages. […] IL-6 is an important inflammatory factor involved in many proinflammatory processes in the body. […] IL-1 plays a central role in mediating the inflammatory response and mediates the activation of secondary inflammatory factors such as IL-6. […] Cytokines play an important role in AA. […] The NLRP3 inflammasome consists of the sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and the effector enzyme pro-caspase-1.

• #38 Pathophysiology of abdominal aortic aneurysm: biomarkers and novel therapeutic targets | Clínica e Investigación en Arteriosclerosis (English Edition)

  https://www.elsevier.es/en-revista-clinica-e-investigacion-arteriosclerosis-english-415-articulo-pathophysiology-abdominal-aortic-aneurysm-biomarkers-S2529912319300385

  The pathophysiology of an AAA is a complex and dynamic process which culminates in the irreversible remodelling of the connective tissue.5 There are four main processes which take place in an AAA: proteolysis, oxidative stress, inflammatory immune response and VSMC apoptosis (Fig. 1), processes which cause the loss of elasticity and resistance of the artery wall and impede the recovery of the normal artery diameter after each pulsation. […] An AAA is characterised by a degradation of the connective tissue, mainly of the elastin fibres, through the activation of various proteases such as plasmin, elastase, cathepsins and matrix metalloproteinases (MMPs), along with a reduction in the expression of elastogenic proteins such as fibulin-5.6,7 All of this causes the loss of elastic properties of the artery wall and artery dilation and alters the homeostasis of the vascular cells. In addition, the artery wall shows a significant inflammatory infiltrate consisting of T- and B-cells, neutrophils and macrophages.8,9 Although the mechanism which triggers this inflammatory process is unknown, it is likely that the soluble peptides derived from the degradation of the components of the extracellular matrix act as chemotactic agents promoting the infiltration of macrophages. The increase in the levels of interleukin (IL)-8, MCP-1 and RANTES would in turn facilitate leucocyte recruitment.

• #39 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.

• #40 Pathology Outlines – Aortic aneurysms

  https://www.pathologyoutlines.com/topic/heartcoronaryarteritis.html

  Increase in matrix metalloproteinase activity leading to extensive proteolysis […] Inflammation […] Inflammatory cell infiltration and activation of proteases (Circ Res 2019;124:607) […] Smooth muscle cell (SMC) apoptosis […] Significant loss or disorganization of smooth muscle cells within the intima media […] Degradation of the aortic wall → weakening of the aortic wall → dilation of the aorta → increased aortic wall stress → further wall weakening and risk of rupture […] Hypertension and atherosclerosis accelerate medial degeneration […] Significant loss of smooth muscle cells is a characteristic process of medial degeneration in aortic aneurysm.

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

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

  In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] In AA, the role of TGF- is still controversial. […] The immune response plays an important role in the course of AA. […] The differentiation of TH1 cells depends on the stimulation of IL-12, which in turn secretes interferon- (IFN-) to promote the activation and recruitment of macrophages. […] IL-6 is an important inflammatory factor involved in many proinflammatory processes in the body. […] IL-1 plays a central role in mediating the inflammatory response and mediates the activation of secondary inflammatory factors such as IL-6. […] Cytokines play an important role in AA. […] The NLRP3 inflammasome consists of the sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and the effector enzyme pro-caspase-1.

• #42 Innovation in pathogenesis and management of aortic aneurysm

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

  Most macrophages found in AAAs come from circulating monocytes, but some are aortic tissue-resident macrophages. Throughout AAA development and progression, macrophages have destructive and reparative roles in extracellular matrix remodeling and promotion and resolution of inflammation, depending on the microenvironmental conditions and the chemokines and cytokines present. […] The presence of TNF-alpha and IL-1 in tissue extracts of AAA is indicative of that infiltrative inflammatory process. […] IL-1 plays a central role in the inflammatory process of aneurysm formation via cascading of signaling pathways and various mechanisms of action. […] The NLRP3 inflammasome, a cytosolic multiprotein complex, serves as a pivotal regulator in the activation of caspase-1, orchestrating the controlled release of pro-inflammatory cytokines IL-1 and IL-18.

• #43 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. […] In the pathophysiology of aortic aneurysms, immune cell accumulation and activation in aneurysmal lesions are the main features associated with inflammation and structural remodeling of the aortic wall. […] Cytokines are crucial contributors to inflammatory alterations during AAA formation, and altered expression and epigenetic changes in cytokines were present in AAA tissue samples. […] The upregulation of TLR2 and its ligands was identified in human AAA tissue, and antagonism of TLR2 in a mouse model decreased the formation and progression of AAA and inhibited chronic inflammation and vascular remodeling. […] Therefore, further studies are needed to clarify the roles of the IL-1 signaling pathway in aortic aneurysms.

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

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

  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). […] The establishment of good animal models is helpful to elucidate the complex pathogenesis, which is used to develop new therapeutic methods or improve endovascular and surgical procedures.

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

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

  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). […] The establishment of good animal models is helpful to elucidate the complex pathogenesis, which is used to develop new therapeutic methods or improve endovascular and surgical procedures.

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

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

  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). […] The establishment of good animal models is helpful to elucidate the complex pathogenesis, which is used to develop new therapeutic methods or improve endovascular and surgical procedures.

• #47 Iron Overload and Abdominal Aortic Aneurysm

  https://www.imrpress.com/journal/RCM/25/10/10.31083/j.rcm2510361/htm

  Accumulating evidence increasingly supports the role of iron metabolism and overload in AAA pathogenesis. It is now believed that iron accumulation may be a causal factor in AAA, rather than a mere consequence. […] Iron overload is implicated in vascular remodeling under certain pathological conditions, including elevated Ang II levels. […] The mechanisms underlying iron deposition in AAA tissues are not completely understood. It is well known that chronic inflammation, oxidative stress, excessive matrix degradation and vascular smooth muscle cell apoptosis are critical factors in AAA histopathology. […] Evidence has shown that high intracellular iron concentrations in macrophages rather than increased systemic iron levels drive inflammation. […] The accumulation of iron in macrophages further promotes MMP production. […] Iron overload can exacerbate lipid peroxidation via the Fenton reaction, inducing ferroptosis, and subsequently resulting in vascular SMCs loss. […] Iron overload is involved in the pathology of AAA, making its early identification and correction a priority for potential clinical benefits.

• #48 175 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.

• #49 Pathogenesis of Abdominal Aortic Aneurysm | IntechOpen

  https://www.intechopen.com/chapters/71452

  Apoptosis is considered an organized and instructed route of cell death while necrosis is regarded as an unorganized disruption of a cell with an additional immune response. […] The role of oxidative stress in the pathogenesis of aortic pathologies such as aortic aneurysm involves pathologic vascular remodeling along with dysfunctional balancing of connective tissue breakdown and synthesis by VSMCs. […] Oxidative stress is a major modulator of MMP formation and can disrupt the corresponding balance of TIMPs that are otherwise crucial to the structural integrity of the extracellular matrix of the arterial wall.

• #50 Pathogenesis of Abdominal Aortic Aneurysm | IntechOpen

  https://www.intechopen.com/chapters/71452

  Apoptosis is considered an organized and instructed route of cell death while necrosis is regarded as an unorganized disruption of a cell with an additional immune response. […] The role of oxidative stress in the pathogenesis of aortic pathologies such as aortic aneurysm involves pathologic vascular remodeling along with dysfunctional balancing of connective tissue breakdown and synthesis by VSMCs. […] Oxidative stress is a major modulator of MMP formation and can disrupt the corresponding balance of TIMPs that are otherwise crucial to the structural integrity of the extracellular matrix of the arterial wall.

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

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

  In AA, ECM degrades and leads to the fragmentation and dilatation of the vessel wall. […] The activity of MMPs is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). […] In AA, the role of TGF- is still controversial. […] The immune response plays an important role in the course of AA. […] The differentiation of TH1 cells depends on the stimulation of IL-12, which in turn secretes interferon- (IFN-) to promote the activation and recruitment of macrophages. […] IL-6 is an important inflammatory factor involved in many proinflammatory processes in the body. […] IL-1 plays a central role in mediating the inflammatory response and mediates the activation of secondary inflammatory factors such as IL-6. […] Cytokines play an important role in AA. […] The NLRP3 inflammasome consists of the sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and the effector enzyme pro-caspase-1.

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

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

  Furthermore, these biological mechanisms are thought to initiate the degradation of elastic fibers and alterations in collagen composition, ultimately compromising the structural integrity and reducing the flexibility of the aortic wall. […] 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.

• #53 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. […] Disruption of elastin has been particularly implicated in AAA development and progression, while degradation of collagen is thought to be more important in AAA rupture. […] 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.

• #54

  https://www.jci.org/articles/view/38136

  TGF- regulates many aspects of cellular performance relevant to tissue morphogenesis and homeostasis. Postnatal perturbation of TGF- signaling contributes to the pathogenesis of many disease states, as recently exemplified through the study of Marfan syndrome (MFS), including aortic aneurysm and skeletal muscle myopathy. […] However, the role of TGF- in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF- activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II-induced AAA formation and markedly increases their susceptibility to the disease. […] These results clearly identify a critical role for TGF- in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.

• #55

  https://www.jci.org/articles/view/38136

  Our present results clearly indicate that the recently reported pathogenic role of TGF- activity in Marfan syndrome cannot be extrapolated to Ang II-dependent AAA and that increased TGF- expression in the Ang II-induced mouse model of AAA should be considered as a counterregulatory protective process that is critically required for the preservation of vessel integrity in C57BL/6 mice. […] We propose that because it promotes smooth muscle cell survival, matrix preservation, and anti-inflammatory activities, TGF- is required for the prevention of the prominent vascular inflammation, vascular cell death, and matrix degradation that characterize AAA in humans and that are recapitulated, at least to some extent, in the mouse model of Ang II-induced AAA.

• #56

  https://www.jci.org/articles/view/38136

  Our present results clearly indicate that the recently reported pathogenic role of TGF- activity in Marfan syndrome cannot be extrapolated to Ang II-dependent AAA and that increased TGF- expression in the Ang II-induced mouse model of AAA should be considered as a counterregulatory protective process that is critically required for the preservation of vessel integrity in C57BL/6 mice. […] We propose that because it promotes smooth muscle cell survival, matrix preservation, and anti-inflammatory activities, TGF- is required for the prevention of the prominent vascular inflammation, vascular cell death, and matrix degradation that characterize AAA in humans and that are recapitulated, at least to some extent, in the mouse model of Ang II-induced AAA.

• #57

  https://www.jci.org/articles/view/38136

  Our present results clearly indicate that the recently reported pathogenic role of TGF- activity in Marfan syndrome cannot be extrapolated to Ang II-dependent AAA and that increased TGF- expression in the Ang II-induced mouse model of AAA should be considered as a counterregulatory protective process that is critically required for the preservation of vessel integrity in C57BL/6 mice. […] We propose that because it promotes smooth muscle cell survival, matrix preservation, and anti-inflammatory activities, TGF- is required for the prevention of the prominent vascular inflammation, vascular cell death, and matrix degradation that characterize AAA in humans and that are recapitulated, at least to some extent, in the mouse model of Ang II-induced AAA.

• #58 Improved insights in the pathogenesis of abdominal aortic aneurysm unlock new therapeutic avenues

  https://www.escardio.org/Working-groups/Working-Group-on-Aorta-and-Peripheral-Vascular-Diseases/Publications/improved-insights-in-the-pathogenesis-of-abdominal-aortic-aneurysm-unlock-new-therapeutic-avenues

  From the identified AAA risk loci, it becomes evident that lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation are key mechanisms in AAA pathogenesis. […] In particular, the results strongly highlight the critical role of lipids and lipid metabolism in AAA pathogenesis, rendering them key therapeutic targets.

• #59 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. […] The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. […] Aortic aneurysm development and progression have been directly associated with a deficiency of elastin as well as a loss of collagen type 1. […] The elastin-to-collagen ratio is also significantly higher in aneurysmal abdominal aortas compared to healthy abdominal aortas. […] While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.

• #60 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. […] The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. […] Aortic aneurysm development and progression have been directly associated with a deficiency of elastin as well as a loss of collagen type 1. […] The elastin-to-collagen ratio is also significantly higher in aneurysmal abdominal aortas compared to healthy abdominal aortas. […] While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.

• #61 About Aortic Aneurysm | Heart Disease | CDC

  https://www.cdc.gov/heart-disease/about/aortic-aneurysm.html

  Aortic aneurysms can dissect or rupture: […] The force of blood pumping can split the layers of the artery wall, allowing blood to leak in between them. This process is called a dissection. […] The aneurysm can burst completely, causing bleeding inside the body. This is called a rupture. […] Dissections and ruptures are the cause of most deaths from aortic aneurysms. […] Thoracic aortic aneurysms are usually caused by high blood pressure or sudden injury. Sometimes people with inherited connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome, get thoracic aortic aneurysms. […] Abdominal aortic aneurysms are usually caused by atherosclerosis (hardened arteries), but infection or injury can also cause them. […] Diseases and unhealthy behaviors that damage your heart and blood vessels also increase your risk for aortic aneurysm. Smoking is the most important behavior related to aortic aneurysm.

• #62 About Aortic Aneurysm | Heart Disease | CDC

  https://www.cdc.gov/heart-disease/about/aortic-aneurysm.html

  Aortic aneurysms can dissect or rupture: […] The force of blood pumping can split the layers of the artery wall, allowing blood to leak in between them. This process is called a dissection. […] The aneurysm can burst completely, causing bleeding inside the body. This is called a rupture. […] Dissections and ruptures are the cause of most deaths from aortic aneurysms. […] Thoracic aortic aneurysms are usually caused by high blood pressure or sudden injury. Sometimes people with inherited connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome, get thoracic aortic aneurysms. […] Abdominal aortic aneurysms are usually caused by atherosclerosis (hardened arteries), but infection or injury can also cause them. […] Diseases and unhealthy behaviors that damage your heart and blood vessels also increase your risk for aortic aneurysm. Smoking is the most important behavior related to aortic aneurysm.

• #63 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.

• #64 Pathogenesis and management of abdominal aortic aneurysm

  https://researchonline.jcu.edu.au/80329/

  Abdominal aortic aneurysm (AAA) causes 170 000 deaths annually worldwide. […] This review outlines research on AAA pathogenesis and therapies to limit AAA growth. […] Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. […] In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

• #65 Improved insights in the pathogenesis of abdominal aortic aneurysm unlock new therapeutic avenues

  https://www.escardio.org/Working-groups/Working-Group-on-Aorta-and-Peripheral-Vascular-Diseases/Publications/improved-insights-in-the-pathogenesis-of-abdominal-aortic-aneurysm-unlock-new-therapeutic-avenues

  From the identified AAA risk loci, it becomes evident that lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation are key mechanisms in AAA pathogenesis. […] In particular, the results strongly highlight the critical role of lipids and lipid metabolism in AAA pathogenesis, rendering them key therapeutic targets.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

• #67 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. […] Disruption of elastin has been particularly implicated in AAA development and progression, while degradation of collagen is thought to be more important in AAA rupture. […] 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.

• #68

  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.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

• #70 Pathology Outlines – Aortic aneurysms

  https://www.pathologyoutlines.com/topic/heartcoronaryarteritis.html

  Increase in matrix metalloproteinase activity leading to extensive proteolysis […] Inflammation […] Inflammatory cell infiltration and activation of proteases (Circ Res 2019;124:607) […] Smooth muscle cell (SMC) apoptosis […] Significant loss or disorganization of smooth muscle cells within the intima media […] Degradation of the aortic wall → weakening of the aortic wall → dilation of the aorta → increased aortic wall stress → further wall weakening and risk of rupture […] Hypertension and atherosclerosis accelerate medial degeneration […] Significant loss of smooth muscle cells is a characteristic process of medial degeneration in aortic aneurysm.

• #71 175 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 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.

• #72 Pathophysiology of abdominal aortic aneurysm: biomarkers and novel therapeutic targets | Clínica e Investigación en Arteriosclerosis (English Edition)

  https://www.elsevier.es/en-revista-clinica-e-investigacion-arteriosclerosis-english-415-articulo-pathophysiology-abdominal-aortic-aneurysm-biomarkers-S2529912319300385

  The pathophysiology of an AAA is a complex and dynamic process which culminates in the irreversible remodelling of the connective tissue.5 There are four main processes which take place in an AAA: proteolysis, oxidative stress, inflammatory immune response and VSMC apoptosis (Fig. 1), processes which cause the loss of elasticity and resistance of the artery wall and impede the recovery of the normal artery diameter after each pulsation. […] An AAA is characterised by a degradation of the connective tissue, mainly of the elastin fibres, through the activation of various proteases such as plasmin, elastase, cathepsins and matrix metalloproteinases (MMPs), along with a reduction in the expression of elastogenic proteins such as fibulin-5.6,7 All of this causes the loss of elastic properties of the artery wall and artery dilation and alters the homeostasis of the vascular cells. In addition, the artery wall shows a significant inflammatory infiltrate consisting of T- and B-cells, neutrophils and macrophages.8,9 Although the mechanism which triggers this inflammatory process is unknown, it is likely that the soluble peptides derived from the degradation of the components of the extracellular matrix act as chemotactic agents promoting the infiltration of macrophages. The increase in the levels of interleukin (IL)-8, MCP-1 and RANTES would in turn facilitate leucocyte recruitment.

• #73 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.

• #74 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  Smoking is a well-established and the most important risk factor for AAA, playing even greater role in AAA than atherosclerosis. […] Several studies have suggested that microorganisms, including Chlamydia, Mycoplasma pneumoniae, Helicobacter pylori, human cytomegalovirus, herpes simplex virus, Borrelia burgdorferi sensu lato (sl) and different oral bacteria may serve as possible triggers for the development of AAAs.

• #75 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. […] Disruption of elastin has been particularly implicated in AAA development and progression, while degradation of collagen is thought to be more important in AAA rupture. […] 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.

• #76 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  Smoking is a well-established and the most important risk factor for AAA, playing even greater role in AAA than atherosclerosis. […] Several studies have suggested that microorganisms, including Chlamydia, Mycoplasma pneumoniae, Helicobacter pylori, human cytomegalovirus, herpes simplex virus, Borrelia burgdorferi sensu lato (sl) and different oral bacteria may serve as possible triggers for the development of AAAs.

• #77 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

  Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. […] AAA progression towards rupture is not linear, but usually presents periods of stability alternating with periods of growth (staccato growth). […] Neutrophil activation leads to the release of markers measurable in plasma of patients with AAA, such as MMP-9, elastase-1 antitrypsin complexes and myeloperoxidase. […] Recent epidemiological data indicate that chronic periodontitis, the most common form of periodontal disease, is associated with occlusive atherothrombotic plaque 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.

• #78 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

  We have shown that stimulation of human neutrophils by P. gingivalis led to NET production, reflected by an increased cell-free DNA (cf-DNA) concentration in the culture supernatant and by histone exposure/modifications. […] In conclusion, the results of the present study indicate that P. gingivalis accelerates AAA progression via recruitment and activation of neutrophils, leading to production of NETs which are detectable in the plasma of AAA subjects.

• #79 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

• #80 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

• #81 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

• #82 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

• #83 Understanding the pathogenesis of abdominal aortic aneurysms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4829576/

  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%. […] 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. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation, and oxidative stress. […] The genome-wide expression analyses have demonstrated a large number of genes with altered mRNA levels in the AAA tissue. A large fraction of these genes belong to immunological pathways such as the Natural Killer Cell Cytotoxicity pathway.

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

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

  Furthermore, these biological mechanisms are thought to initiate the degradation of elastic fibers and alterations in collagen composition, ultimately compromising the structural integrity and reducing the flexibility of the aortic wall. […] 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.

• #85 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. […] The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. […] Aortic aneurysm development and progression have been directly associated with a deficiency of elastin as well as a loss of collagen type 1. […] The elastin-to-collagen ratio is also significantly higher in aneurysmal abdominal aortas compared to healthy abdominal aortas. […] While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology.

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

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

  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. […] A dissecting aneurysm, also called aortic dissection (AD), is caused by rupture of the aorta, which flows from the inner hole to the middle layer, causing the wall to be disformed and the blood flow to extend along the longitudinal axis. […] The various changes in VSMCs are an important cause of AA formation. […] VSMCs are highly plastic and can switch between two phenotypes. […] The apoptosis of VSMCs can be found in the aortas of AA patients and AA model mice. […] 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.

• #87 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. Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment. […] The underlying problem with aneurysm disease is weakening of the aortic wall, leading to progressive dilation. If not treated in time, the aortic aneurysm eventually ruptures. An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall. […] In the past 30 years, considerable progress has been made in the research of the pathogenesis of aneurysms under multidisciplinary efforts involving molecular and cellular biology and solid and fluid mechanics.

• #88 Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development

  https://www.mdpi.com/2075-4418/13/2/253

  Aortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. […] In this article, we reviewed the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. […] The identification of the subcellular mechanisms and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. […] Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. […] The incidence of thoracic aneurysm is much lower and their formation may be linked to a heritable pattern as one in five patients diagnosed with thoracic aneurysm has a family history of the same pathology.

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