Extracellular Matrix Remodeling Biomarkers in Coronary Artery Disease

Abstract

Atherosclerosis and one of its most serious consequences, coronary artery disease, are important sources of morbidity and mortality globally, necessitating early detection and treatment. Considering their complex pathophysiology, including several harmful processes, a comprehensive approach to diagnosis, prognosis, and therapy is very desirable. Extracellular matrix remodeling is a major component of this dangerous cascade, including the cleavage of constituents (collagen, elastin, proteoglycans) and the propagation or exacerbation of the inflammatory response. Several extracellular matrix degradation indicators have been hypothesized to correlate with the existence, severity, and prognosis of coronary artery disease. The potency of matrix metalloproteinases, notably collagenases and gelatinases, has been the most thoroughly investigated in clinical studies. Stromelysins, matrilysins, transmembrane matrix metalloproteinases, collagen and laminin turnover indicators, as well as fibronectin, have also been studied to a lesser level. Among the most well-studied markers, MMP-1, MMP-2, MMP-8, and MMP-9 have been found increased in patients with cardiovascular risk factors such as metabolic syndrome, its components (obesity, dyslipidemia, diabetes mellitus), and smoking. Increasing concentrations are detected in acute coronary syndromes compared to stable angina pectoris and healthy control groups. It should also be stressed that those extracellular matrix biomarkers may also be detected in high concentrations in other vascular pathologies such as peripheral artery disease, carotid artery disease, aortic aneurysms, and dissections. Despite the advances gained, future research should focus on their importance and, more crucially, their added utility as biomarkers in identifying persons at risk of developing overt coronary artery disease. At the same time, determining the prognosis of coronary artery disease patients using such biomarkers may be important for their adequate care.

Evaluation of MMP-9, IL-6, TNF-α levels and peripheral blood mononuclear cells genes expression of MMP-9 and TIMP-1 in Iranian patients with coronary artery disease

“…Our results agree with previous studies that have also revealed that MMP-1 and MMP-9 levels increased in individuals with CAD. 9 , 22 However, contrary to our finding, some studies showed no significant difference between MMP-9 in CAD patients and controls. 29 Our findings indicate no significant variation in TIMP-1 gene expression between both groups.…”

“…Therefore, this association between both genes revealed a molecular mechanism for modulation of MMP-9 gene expression and activity ( P < 0.05). 9 - 14 …”

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment

“…Hemodynamic factors like shear stress and cyclic strain exert mechanical strain on the plaque, leading to cap thinning and eventual rupture. Moreover, prolonged inflammation within the plaque prompts the release of proteolytic enzymes, particularly matrix metalloproteinases (MMPs), which degrade components of the extracellular matrix [ 2 ]. An imbalance between MMPs and their inhibitors weakens the fibrous cap, rendering it more susceptible to rupture [ 2 ].…”

“…Moreover, prolonged inflammation within the plaque prompts the release of proteolytic enzymes, particularly matrix metalloproteinases (MMPs), which degrade components of the extracellular matrix [ 2 ]. An imbalance between MMPs and their inhibitors weakens the fibrous cap, rendering it more susceptible to rupture [ 2 ]. Inflammation plays a pivotal role in both the initiation and progression of PR.…”

Inflammasomes in Atherosclerosis—From Pathophysiology to Treatment

“…Despite extensive research, the intricacies of atherosclerotic development and progression have proven to be multifaceted and involve complex interactions between various cell types, inflammatory mediators, and genetic factors [4,5]. In recent years, the recognition of the crucial role played by inflammasomes in the pathophysiology of atherosclerosis has emerged as a promising avenue for novel therapeutic interventions [6].…”