Materiały źródłowe

• #1 Thoracic Aorta Aneurysm – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554567/

  Both biochemical and mechanical factors lead to the formation of thoracic aortic aneurysms. The discrepancy between the wall structure elements, including elastin and collagen, proteoglycans, and proteolytic and inflammatory mediators (transforming growth factor-B [TGF-B]), leads to wall weakness and expansion. […] Changes in aortic wall compliance lead to increased stress on the wall as per Laplace’s law (tension= pressure x radius) during a systolic impulse and can further exacerbate wall weakness and lead to the formation of an aneurysm. Intimal atherosclerosis in the descending aorta can further exacerbate medial degeneration. […] A mycotic aneurysm can occur due to an infection damaging an area in the aortic wall.

• #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.

• #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. […] The thoracic aortic aneurysm has been termed cystic medial necrosis which is currently considered as a misnomer because the histopathology of the disease is not characterized by necrosis or cysts. The term medial degeneration is more accurate as the process involves disruption of elastic fibers and accumulation of proteoglycans.

• #4 Ascending aortic aneurysms: pathophysiology and indications for surgery

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-10/Ascending-aortic-aneurysms-pathophysiology-and-indications-for-surgery

  Ascending aortic aneurysms may be fatal due to their liability to dissect or rupture. Understanding the pathophysiology of ascending aortic aneurysms can help reduce the morbidity and mortality from aortic dissections or ruptures by indicating timely elective surgery. […] An ascending aortic aneurysm is an enlargement (in width and/or in length) of a weakened area in the ascending aorta. Whereas other aneurysms of the aorta are associated with atherosclerosis, aneurysms of the ascending aorta are mostly associated with degenerative changes in elastic media. Degenerative processes in ascending aorta – cystic medial degeneration – affect the medial layer by varying degrees of elastic fibre fragmentation and smooth muscle loss. […] The aorta in Marfan’s syndrome exhibits the typical features of cystic medial degeneration with disruption of elastic fibres and fibrosis of media.

• #5 Thoracic Aneurysm: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/761627-overview

  Thoracic aortic aneurysm most commonly results from degeneration of the media of the aortic wall as well as from local hemodynamic forces. […] Degenerative changes in the wall of the aorta lead to cystic medial necrosis. This causes damage to collagen and elastin, loss of smooth muscle cells, and increased amounts of basophilic ground substance in the medial (elastic) layer of the aorta. […] Weakening of the aortic wall is compounded by increased shear stress, especially in the ascending aorta. This segment of the aorta is most exposed to the pressure of each cardiac systole (dP/dt) as well as the dynamic heart motion transmitted from each cardiac cycle. […] Although atherosclerotic disease is often present in patients with thoracic aortic aneurysm (TAA), it may only play a minor causal role in the pathogenesis of aneurysm development.

• #6 Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

  https://www.mdpi.com/1422-0067/25/2/901

  The major pathological features of human TAA include endothelial dysfunction, elastin fragmentation, loss of VSMCs via increased apoptosis, increased deposition of proteoglycans in the tunica media, and excessive accumulation of collagen (vascular fibrosis). […] These changes are often accompanied by an increase in inflammation, oxidative stress, and matrix metalloproteinases (MMPs). […] The VSMC-elastin-contractile unit is a functional and structural unit in the tunica media and plays a vital role in maintaining the structural integrity and function of the thoracic aortic wall. […] As the VSMC-elastin-contractile unit is vital in maintaining aortic integrity, defects in the proteins involved in the pathway could lead to TAA formation. […] VSMC apoptosis has been shown in both human and mouse TAAs.

• #7 Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

  https://www.mdpi.com/1422-0067/25/2/901

  The contribution of inflammation and reactive oxygen species to TAA pathogenesis has been reviewed previously. […] An increase in glycosaminoglycans and proteoglycans in the thoracic aorta leads to swelling of the aortic wall and an increase in mechanical stress, consequently triggering weakening of the aortic wall. […] TGFβ is secreted as large latent complexes which are composed of TGFβ, latency-associated peptide, and latent TGFβ binding protein. […] TGFβ binds to its TGFβ receptor type 2 (TGFBR2) on the cell surface, and the latter recruits and phosphorylates TGFβ receptor type 1 (TGFBR1). […] The current understanding of the role of TGFβ in TAA is stage-specific: TGFβ protects against TAA at early stages of the disease, and it promotes disease progression at late stages.

• #8 Pathology Outlines – Aortic aneurysms

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

  Medial degeneration, led by 3 interconnected processes (Cardiovasc Pathol 2016;25:432) […] Excessive extracellular matrix (ECM) degradation […] Disruption of elastin and collagen homeostasis […] Increase in matrix metalloproteinase activity leading to extensive proteolysis […] Inflammation […] Inflammatory cell infiltration and activation of proteases (Circ Res 2019;124:607) […] Neovascularization […] 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.

• #9 Aortic aneurysm – Wikipedia

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

  An aortic aneurysm can occur as a result of trauma, infection, or, most commonly, from an intrinsic abnormality in the elastin and collagen components of the aortic wall. 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.

• #10 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.

• #11 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.

• #12 Genes in thoracic aortic aneurysms/dissections – do they matter? – De Backer- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/1403/html

  Fortunately, recent developments have changed this insight and it is now recognised that fibrillin-1 fibres also play an important functional role in the complex TGF pathway. […] Since the large latent complex binds TGF, abnormal fibrillin-1 fibres will lead to failed matrix sequestration of the latent TGF complex and hence increase amounts of active TGF, which is in turn at the basis of the pleiotropic manifestations in MFS. […] Additional evidence for the involvement of the TGF pathway in aneurismal disease comes from the finding that mutations in several genes that encode different components of the pathway result in aneurysm conditions that have undeniable clinical overlap with MFS. […] It is clear that these disorders are all part of a broad spectrum and it may be more convenient to group them under the term TGF-related vasculopathies.

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

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

  The N-terminal fragment of GSDMD induces a proinflammatory form of programmed cell death referred to as pyroptosis. […] The disruption of intracellular components involved in SMC contractile function also causes heritable thoracic aortic diseases. […] The elastin-SMC contractile unit in the aorta is a functional and structural element that responds to pulsatile blood pressure and flow; thus, mutations in genes involved in the integrity of the ECM and vascular SMC contraction have been identified in the majority of the heritable risk factors for thoracic aortic diseases.

• #14

  https://link.springer.com/article/10.1007/s00395-024-01053-1

  Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA. […] Once the ECMVSMC network is disrupted, mechanosensing and mechano-signaling are impaired, leading to VSMC phenotype switching. […] A compromised structure and function of the ECM leads to mechanical abnormalities and functional changes at the tissue level associated with aortic disease. […] Progressive loss of arterial wall strength eventually culminates in the development of ATAA and even ATAAD. […] We highlight gaps in current diagnostic approaches, as well as recommend potential clinical biomarkers that may contribute to advancing our understanding of the development of early-stage ATAA, ultimately to predict and prevent morbidity and mortality associated with ATAAD.

• #15

  https://www.jci.org/articles/view/182554

  Aortic aneurysms (AAs) can occur in any segment of the aorta, including thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs). AA typically remains asymptomatic until emergent, and lethal complications such as dissection or rupture occur. […] AA pathogenesis is complex and involves several underlying mechanisms. TAAs have a more robust genetic background than AAAs. Both TAAs and AAAs share common features, including aortic inflammation and the phenotypic switch and/or loss of vascular smooth muscle cells (VSMCs). Inflammation in AA involves the infiltration of inflammatory cells, including macrophages and T lymphocytes. CD4+ and CD8+ T cells, particularly CD4+ Th cells, drive aortic inflammation by releasing proinflammatory factors such as IFN- that promote chemotaxis of other inflammatory cells. These processes induce metalloproteinase expression, which contributes to AA formation and progression by promoting extracellular matrix degradation and VSMC phenotypic switching, ultimately weakening the aortic wall.

• #16 Etiology and Pathogenesis of Aortic Aneurysm | IntechOpen

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

  Histological examination demonstrates that pathophysiological processes in aortic aneurysm involve all layers of the aortic wall, contrasting to those observed in occlusive atherosclerosis. […] 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. […] 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.

• #17

  https://link.springer.com/article/10.1007/s00395-024-01053-1

  The major histopathological features associated with ATAA are abnormalities of cellular and matrix constituents of the media. These include elastin degradation and fragmentation, collagen disorganization, and loss of VSMC number. […] In ATAA, dysfunction of VSMCs causes an imbalance between the production of active MMPs, especially MMP-2 and MMP-9, and a decreased expression of TIMPs, mainly TIMP-1. […] This, in turn, facilitates the disengagement of VSMCs resulting in aortic tissue remodeling. […] The disruption of elastin-VSMC connections plays a critical role in aneurysm formation, not only by damaging the structural integrity of the aortic wall but also by altering cellular processes such as mechanotransduction and cytoskeletal remodeling of VSMCs. […] High WSS is a frictional force at the EC surface produced by blood flow which induces impaired mechanotransduction leading to vascular remodeling and potentially ATAA formation.

• #18 Thoracic aortic aneurysm – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/thoracic-aortic-aneurysm/symptoms-causes/syc-20350188

  A thoracic aortic aneurysm is a weakened area in the upper part of the body’s main artery, called the aorta. […] A thoracic aortic aneurysm occurs when a weak spot in the wall of the aorta begins to bulge. […] Causes of thoracic aortic aneurysms may include: Atherosclerosis. A buildup of fats, cholesterol, and other substances in and on the artery walls causes the arteries to get stiff. Over time, the walls of the arteries may get weak. High blood pressure and high cholesterol increase the risk of atherosclerosis, especially in older people. […] Genetic conditions. Aortic aneurysms in younger people are often caused by changes in genes. A genetic condition called Marfan syndrome can weaken the wall of the aorta. […] Blood vessel inflammation. Conditions that cause irritation and swelling of blood vessels, such as Takayasu arteritis and giant cell arteritis, are associated with thoracic aortic aneurysms.

• #19 Thoracic Aortic Aneurysm: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17552-aorta-thoracic-aortic-aneurysm

  A thoracic aortic aneurysm is a bulge in the part of your aorta that runs through your chest. It forms when your aorta wall grows weak from plaque, connective tissue disorders or other factors. […] Atherosclerosis is the most common cause of thoracic aortic aneurysms. Thats because plaque buildup weakens your aortas walls over time, making aneurysms more likely to develop. […] Factors like plaque buildup or connective tissue diseases can weaken your aortas walls and make them vulnerable to aneurysm formation. […] An ACTA2 mutation can cause your aortas walls to stretch out farther than they should when blood pushes through. […] A thoracic aortic aneurysm is a serious medical condition. Possible complications include: Aneurysm rupture, Aortic dissection, Blood clots that form at the aneurysm site and travel elsewhere in your body (thromboembolism). Such clots can cause a stroke or mesenteric ischemia.

• #20 Genes in thoracic aortic aneurysms/dissections – do they matter? – De Backer- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/1403/html

  Increased TGF signalling has also been reported in human aortic specimens of patients with isolated TAAD and underlying ACTA2 or MYH11 mutations. The exact link is not yet fully understood but links between the cytoskeleton and many aspects of the TGF signalling pathway have been established, including trafficking and activity of TGF receptors and signalling effectors.

• #21 Thoracic aortic aneurysm – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/thoracic-aortic-aneurysm/symptoms-causes/syc-20350188

  Bicuspid aortic valve. Usually the valve between the lower left heart chamber and the aorta has three flaps. A bicuspid valve has only two. People who are born with a bicuspid aortic valve are more likely to get a thoracic aneurysm. […] If you’re at risk of an aortic aneurysm, you might get medicines to lower your blood pressure and relieve stress on weakened arteries. […] Possible complications of a thoracic aortic aneurysm are: A tear in the wall of the aorta, also called an aortic dissection. This life-threatening condition causes bleeding into and along the aortic wall. Emergency surgery is needed to prevent death. […] Rupture of the body’s main artery, called an aortic rupture. If a tear in the aorta causes bleeding outside the aorta, it’s called an aortic rupture. This also is a life-threatening condition that needs treatment right away. In general, the larger the aneurysm, the greater the risk of rupture.

• #22 Identification of immune-related signatures and pathogenesis differences between thoracic aortic aneurysm patients with bicuspid versus tricuspid valves via weighted gene co-expression network analysis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0292673

  Thoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. […] However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients. […] TAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.

• #23 Ascending aortic aneurysms: pathophysiology and indications for surgery

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-10/Ascending-aortic-aneurysms-pathophysiology-and-indications-for-surgery

  Aneurysmal degeneration of the ascending aorta may also be caused by atherosclerosis, although atherosclerosis less commonly affects the ascending aorta. Atherosclerotic processes in aortic media cause extensive disruption of elastic fibres and smooth muscle cells which may then be replaced by extracellular matrix and lipids. […] Systemic arteritis such as Takayasu’s arteritis, Kawasaki disease, Behet’s disease or giant cell arteritis may involve ascending aorta and initiate formation of an aneurysm. An aseptic inflammatory process in the medial layer of the aorta is presumed to induce medial destruction, which leads to weakening of the aortic wall and potential aneurysm formation or dissection.

• #24 Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm

  https://www.mdpi.com/2075-1729/11/12/1395

  Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. […] We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis. […] The morphological features of the thoracic and abdominal aorta can explain the differences between the AAA and TAA pathogenesis. […] Thus, ascending aortic aneurysm is primarily associated with cystic degeneration of the middle layer of the blood vessel (tunica media) — a process that can occur as an integral element of the body’s natural aging.

• #25 Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex vivo treatment | SpringerPlus | Full Text

  https://springerplus.springeropen.com/articles/10.1186/s40064-015-0976-9

  Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). […] The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. […] Aneurysms are degenerative pathologies caused by the destruction of the extracellular matrix, including elastic fibers. […] Their etiopathology is multifactorial and is still not well-defined. Atherosclerosis is considered the most common cause of AAs, even though several reports have strongly suggested that AAs may be caused by genetic factors, more precisely for TAA.

• #26 Multi-omics in thoracic aortic aneurysm: the complex road to the simplification | Cell & Bioscience | Full Text

  https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01080-w

  Literature suggests that the alterations in TAA mediators frequently involve members of pro-fibrotic process (i.e., TGF- signaling pathways) or proteins associated with cell/extracellular structures (e.g., aggrecans). Further analyses often reported the importance in TAA of processes as inflammation (PCR, CD3, leukotriene compounds), oxidative stress (chromatin OXPHOS, fatty acids), mitochondrial respiration and glycolysis/gluconeogenesis (e.g., PPARs and HIF1a). Of note, more recent metabolomics studies added novel molecular markers to the list of TAA-specific detrimental mediators (proteoglycans). […] Importantly, recent progresses in metabolomics highlighted novel potential and unprecedented marks in TAA diagnosis and therapy. […] The various subtypes of thoracic aortopathy contribute to increase the intricacy of this pathological scenario as well as the complexity of the biological system, in which genetic factors, physical-mechanical stimuli and comorbidities with other pathologies may play a significative role.

• #27 Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm

  https://www.mdpi.com/2075-1729/11/12/1395

  Therefore, based on the available data, a unifying hypothesis can be formulated, according to which mitochondrial dysfunction can have a double role in TAA development. […] These pathological changes can be based on two pathological processes. First, mitochondria can activate pro-inflammatory reaction through mtDAMP release, followed by chronic inflammation and changes of ECM structure. Second, mtROS generation can play a key role in fibrogenesis.

• #28 Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis

  https://www.spandidos-publications.com/10.3892/mmr.2019.10761

  Thoracic aortic aneurysm (TAA) and thoracic aortic dissection (TAD) are aortic diseases known as silent killers. […] The primary cause of aortic diseases is the degeneration of the aortic media layer due to hereditary and environmental factors. […] The process of the degeneration of the media layer, consisting of elastin and smooth muscle cells (SMC) involves changes to the SMC phenotype, loss of elastin layers and the increased production of matrix metalloproteinases and proteoglycans. […] Hsa-miR-143-3p is one of the most important miRNAs expressed by vascular SMCs (VSMC) and interacts with Kirsten rat sarcoma viral oncogene homolog (KRAS) and mitogen-activated protein kinases (MAPKs), associated with the pathogenesis of aortic diseases. […] This miRNA regulates the MAPK pathways that induce TAA formation via non-canonical transforming growth factor signaling.

• #29 Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis

  https://www.spandidos-publications.com/10.3892/mmr.2019.10761

  The increased expression level of hsa-miR-143-3p results in a decrease in KRAS expression and VSMC proliferation. […] The results of the MAPK14 ROC analysis demonstrated that MAPK14 may be an important biomarker in the differentiation between TAA and TAD groups. […] The present study revealed that the increase in expression levels of hsa-miR-143-3p and hsa-miR-22 candidate miRNAs were statistically significantly higher in the TAA group compared with the control group. […] Therefore, it may be suggested that, at the molecular level, hsa-miR-143-3p regulates VSMC proliferation and endothelial cell survival rate by targeting KRAS and MAPK7. […] The expression level of MAPK14 decreased in the TAD group while it increased in the TAA group.

• #30

  https://grantome.com/grant/NIH/R56-HL141130-01

  Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening manifestation of diverse vascular smooth muscle cell (VSMC) or extracellular matrix (ECM) disorders. The histopathological hallmark of TAAD is aortic medial degeneration (AMD), characterized by proteoglycan accumulation (pooling), elastic fiber fragmentation and VSMC degeneration. […] We hypothesize that accumulation of the large aggregating proteoglycans aggrecan and versican is a consistent pathologic feature of TAAD, alters VSMC phenotype and survival to compromise aorta function, and could arise from reduced proteolysis. […] Immunostaining of normal and TAAD ascending aortas collected prospectively at the Cleveland Clinic revealed an unexpected, massive increase of aggrecan and versican in TAAD aortas. […] The specific aims are: 1. To characterize proteoglycan dysregulation in human TAAD using quantitative tandem mass spectrometry approaches and investigate its correlation to disease severity. 2. To determine the pathogenic mechanisms by which reduced proteoglycan turnover by ADAMTS1 contributes to TAAD and the impact of excess aggrecan on VSMC function.

• #31 Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

  https://www.mdpi.com/1422-0067/25/2/901

  Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. […] Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. […] The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. […] Considering the potential limitations of open surgical repair and TEVAR and the lack of effective pharmacological therapies for TAA, it is a major medical need to understand the cellular and molecular mechanisms underlying TAA pathogenesis better and to develop new therapies including those to prevent endoleak following TEVAR.

• #32 Multi-omics in thoracic aortic aneurysm: the complex road to the simplification | Cell & Bioscience | Full Text

  https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01080-w

  To the end of rationalization, simplification, as well as targeting the research for etiological mechanisms of TAA, the adoption of different -omics disciplines seems to be mandatory. […] This process determines, in an apparently counterintuitive manner, the generation of a multitude of data, which allows unmasking numerous pathological alterations in comparison with controls. […] The multitude of available -omics and the dimension of generated data may further complicate already unclear pathological pictures, by tackling the problem through excessive layers. For this reason, several studies, to date, employ a combination of two or three of -omics approaches to achieve a more focused analysis. […] Overall, as integrative multi-omics approaches are powerful tool to arise new relevant information from tangled molecular scenarios, new studies combining multiple -omics layers on TAA are strongly desired to identify key players on its pathogenesis and to propose effective therapeutic strategies or drugs.

• #33 Etiology, pathogenesis and management of thoracic aortic aneurysm | Nature Reviews Cardiology

  https://www.nature.com/articles/ncpcardio0937

  Given the growing proportion of elderly people in Western societies and the increasing prevalence of chronic hypertension, the management of aneurysmal aortic disease is an ever growing challenge. […] Although degenerative changes in the aortic wall are common to thoracic aortic aneurysm (TAA) and to various types of dissection in general, TAA can result from specific heritable disorders of connective tissues. […] A broad variety of inflammatory and infectious disorders, clustered under the term 'aortitis’, can occasionally cause thoracic aortic aneurysm. […] Oxidative stress in the pathogenesis of thoracic aortic aneurysm: protective role of statin and angiotensin II type I receptor blocker. […] Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome.

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