Regulation of Myocardial Extracellular Matrix Dynamic Changes in Myocardial Infarction and Postinfarct Remodeling

Abstract

The article represents literature review dedicated to molecular and cellular mechanisms underlying clinical manifestations and outcomes of acute myocardial infarction. Extracellular matrix adaptive changes are described in detail as one of the most important factors contributing to healing of damaged myocardium and post-infarction cardiac remodeling. Extracellular matrix is reviewed as dynamic constantly remodeling structure that plays a pivotal role in myocardial repair. The role of matrix metalloproteinases and their tissue inhibitors in fragmentation and degradation of extracellular matrix as well as in myocardium healing is discussed. This review provides current information about fibroblasts activity, the role of growth factors, particularly transforming growth factor β and cardiotrophin-1, colony-stimulating factors, adipokines and gastrointestinal hormones, various matricellular proteins. In conclusion considering the fact that dynamic transformation of extracellular matrix after myocardial ischemic damage plays a pivotal role in myocardial infarction outcomes and prognosis, we suggest a high importance of further investigation of mechanisms underlying extracellular matrix remodeling and cell-matrix interactions in cardiovascular diseases.

Neutrophil degranulation and myocardial infarction

“…The overproduction and accumulation of MMPs cause imbalance expression between MMPs and tissue inhibitors of metalloproteinases, which contributes to the development of acute heart failure and acute aneurysm in the acute stage and progress of malignant cardiac remodeling and heart failure in the post-MI period. MMPs are composed of five subgroups according to their localization and substrate specificity containing collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, enamelysin, and others [ 103 , 104 ]. MMP-8, also known as collagenase-2 or neutrophil collagenase, is mainly generated by neutrophils and macrophages [ 105 ].…”

Identification and Interaction Analysis of Molecular Markers in Myocardial Infarction by Integrated Bioinformatics Analysis

“…In the present investigation, a GO and pathway enrichment analysis was conducted to further understand the regulatory roles of DEGs in MI. Immune system [46], innate immune system [47], neutrophil degranulation [48], toll-like receptor cascades [49], metabolism of amino acids and derivatives [50], neuronal system [51], extracellular matrix organization [52], degradation of the extracellular matrix [53], diseases of glycosylation [54], response to stimulus [55], cell communication [56], cell periphery [57], membrane [58], anatomical structure development [59] and plasma membrane [60] were responsible for progression of MI. PLA2G2A [61], CCL23 [62], CD53 [63], TREML4 [64], TREM2 [65], CD180 [66], HPSE (heparanase) [67], CELA2A [68], TNFRSF4 [69], AMBP (alpha-1-microglobulin/bikunin precursor) [70], SOX18 [71], PANX2 [72], RSPO2 [73], COMP (cartilage oligomeric matrix protein) [74], ASGR1 [75] and NOXA1 [76] are involved in progression of atherosclerosis.…”

Matrix Metalloproteinases in Cardioembolic Stroke: From Background to Complications

“…MMP-8 mRNA increased as early as in 6 h, but MMP-8 protein expression was elevated in 2 weeks and was still detected 16 weeks post-MI [ 60 ]. In the early period of MI, MMPs are enrolled predominantly in the process of the myocardial proteins proteolysis and degradation, subsequently MMPs can modulate inflammation and angiogenesis by regulation of ECM and non-ECM substrates (including aggrecan, hyaluronan receptor CD44, complement C1q, connexin 43, fibrinogen, fibronectin, fibroblast growth factor receptor 1 and interleukin-1β), whereas in the later post-MI stages may contribute to excessive fibrosis and adverse remodeling [ 56 , 60 , 61 ]. The interesting observation was reported in Mmp-7 null mice, in which the levels of connexin-43 were increased following MI.…”

“…The imbalance between MMPs and TIMPs activity with an excessive fibrosis and depletion of correctly functioning cardiomyocytes in later post-MI stage results in maladaptive remodeling of myocardial tissue and leads to the development of progressive heart failure, which is another risk factor of thromboemolism in patients with AF [ 56 , 60 , 61 ]. The wide range of MMPs biological functions may contribute to the formation of optimal or insufficient scar in the process of post-MI healing.…”