Extracellular matrix turnover and signaling during cardiac remodeling following MI: Causes and consequences

Abstract

The concept that extracellular matrix (ECM) turnover occurs during cardiac remodeling is a wellaccepted paradigm. To date, a multitude of studies document that remodeling is accompanied by increases in the synthesis and deposition of ECM components as well as increases in extracellular proteases, especially matrix metalloproteinases (MMPs), which break down ECM components. Further, soluble ECM fragments generated from enzymatic action serve to stimulate cell behavior and have been proposed as candidate plasma biomarkers of cardiac remodeling. This review briefly summarizes our current knowledge base on cardiac ECM turnover following myocardial infarction (MI), but more importantly extends discussion by defining avenues that remain to be explored to drive the ECM remodeling field forward. Specifically, this review will discuss cause and effect roles for the ECM changes observed following MI and the potential role of the ECM changes that may serve as trigger points to regulate remodeling. While the pattern of remodeling following MI is qualititatively similar but quantitively different from various types of injury, the basic theme in remodeling is repeated. Therefore, while we use the MI model as the prototype injury model, the themes discussed here are also relevant to cardiac remodeling due to other types of injury.

Quantitative N-linked Glycoproteomics of Myocardial Ischemia and Reperfusion Injury Reveals Early Remodeling in the Extracellular Environment

“…Remodeling is a complex event defined as "genomic expression resulting in molecular, cellular and interstitial changes that are manifested clinically as changes in size, shape and function of the heart after cardiac injury" (44). The balance between ECM deposition and degradation is critical in the clinical outcome -where deposition is excessive, fibrosis leading to LV heart failure may occur; where degradation is predominant, LV wall thinning leading to rupture is possible (28). Anatomical imaging, such as magnetic resonance imaging, is the reference standard for determining prognosis and therapy following acute myocardial infarction (AMI).…”

“…The ECM provides an organized framework that enforces strict myocyte orientation and structural integrity allowing myocardial contraction and myofibril alignment (27). Following myocardial infarction, the ECM is involved in the process of cardiac remodeling (28). Remodeling is typically described as a process involving three main, overlapping phases: inflammatory, proliferative, and maturation (29).…”

Myocardial fibrosis in response to Angiotensin II is preceded by the recruitment of mesenchymal progenitor cells

“…In models of ischemia, in which there has been myocardial injury or infarction, inflammation has been shown to have a key function in healing and likely participates in the development of fibrosis but its contribution to date has been poorly defined. [30][31][32] The complex interactions between ischemia and the development of fibrosis were not explored in this study.…”

CC chemokine receptor 5 deletion impairs macrophage activation and induces adverse remodeling following myocardial infarction

“…MMPs are critical components of post-MI inflammation, and MMP levels regulate ECM content during scar formation (21,35). In addition to the ECM degrading MMPs, BMP-1 is a metalloproteinase that stimulates collagen crosslinking by activating lysyl oxidase (22).…”