Role of Extracellular Matrix and Inflammation in Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is one of the most dangerous cardiovascular diseases, occurring mainly in men over the age of 55 years. As it is asymptomatic, patients are diagnosed very late, usually when they suffer pain in the abdominal cavity. The late detection of AAA contributes to the high mortality rate. Many environmental, genetic, and molecular factors contribute to the development and subsequent rupture of AAA. Inflammation, apoptosis of smooth muscle cells, and degradation of the extracellular matrix in the AAA wall are believed to be the major molecular processes underlying AAA formation. Until now, no pharmacological treatment has been implemented to prevent the formation of AAA or to cure the disease. Therefore, it is important that patients are diagnosed at a very early stage of the disease. Biomarkers contribute to the assessment of the concentration level, which will help to determine the level and rate of AAA development. The potential biomarkers today include homocysteine, cathepsins, osteopontin, and osteoprotegerin. In this review, we describe the major aspects of molecular processes that take place in the aortic wall during AAA formation. In addition, biomarkers, the monitoring of which will contribute to the prompt diagnosis of AAA patients over the age of 55 years, are described.

The abdominal aortic aneurysm-related disease model based on machine learning predicts immunity and m1A/m5C/m6A/m7G epigenetic regulation

“…In contrast, regulation of autophagy, RNA metabolic process, histone methylation, glycosaminoglycan metabolic process, histone H2A monoubiquitination, interleukin-27-mediated signaling pathway, and regulation of response to DNA damage stimulus were negatively enriched based on limma-based DEGs between AAA and normal samples. It is thought that one of the primary molecular pathways underpinning AAA development is Frontiers in Genetics frontiersin.org inflammation in the AAA wall (Stepien et al, 2022). Therefore, the limma-based DEGs were also believed to be reliable.…”

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

“…A central manifestation of vascular wall injury is extracellular matrix remodeling, which typically occurs in 2 phases (like most tissue injuries) which is acute provisional ECM deposition, followed by a chronic phase characterized by replacement of the injured cellular and matrix elements with interstitial collagenous matrices containing collagen type I, III, V, and VI, FN, osteopontin, tenascin C, and various proteoglycans, such as versican, aggrecan and decorin (ie, vessel wall fibrosis response). 8,12,32,[43][44][45][46][47][48][49][50] Following vascular wall injury, the differentiation and quiescence signals supplied by the healthy vascular ECM are diminished by (1) physical loss of ECM components via ECM proteolysis; (2) exposure of previous hidden integrinbinding sites in the insoluble ECM, termed matricryptic sites 51-53 ; (3) release of ECM fragments with biological activity termed matricryptins 52,[54][55][56][57][58][59] ; (4) deposition of provisional ECM components from plasma leakage 14,26,[60][61][62][63] ; and;(5) synthesis of injury-induced ECM proteins including cellular FN (ie, EDA [FN extra domain A] splice isoform), osteopontin and tenascin C. [64][65][66][67][68][69][70] In the case of vascular wall media injury, these altered matrices serve to induce VSMC de-dedifferentiation (ie, synthetic phenotype) 71 that stimulates these cells to proliferate, invade, and deposit reparative and profibrotic matrices including proteoglycans, hyaluronic acid, and interstitial collagens (such as type I, III, V, and VI). 72 The injured and remodeling matrices also contribute and present key growth factors including TGF (transforming growth ...…”

“…82,83,[122][123][124][125] Further regulators of vascular wall injury include glycated plasma proteins or glycated ECM proteins in diabetes, 126,127 and genetic mutations in the vascular wall ECM genes including elastin, fibrillin-1, fibulins, microfibril associated glycoproteins, as well as the ECM cross-linking protein, LOX. 12,82,101,128,129 Other mediators include oxygen radicals, 130 circulating metabolites like high glucose (in diabetes) 127 or homocysteine 46 and microbial products (ie, microbiome), which can contribute toll-like receptor ligands, including lipopolysaccharide, that affects vascular cell responses in part due to macrophage production of the proinflammatory mediators, IL-1β, and TNFα. 117,118,[131][132][133] In the next sections, we will present specific examples that highlight some of the unique features of these distinct but related vascular disease states where ECM remodeling plays an important pathogenic role.…”

A Molecular (Not Very Becoming) Picture of Stressed Arteries and Heart, with Some Therapeutic Hope

“…These two contributions have brought the cardio-renal continuum into the hereby sketched molecular picture. Besides, a review publication has outlined the major mechanisms involved in Abdominal Aortic Aneurysm (AAA), a difficult-to-diagnose latent CVD, including inflammation, smooth muscle cells’ apoptosis, and the degradation of the extracellular matrix [ 9 ].…”