Extracellular matrix roles during cardiac repair

Abstract

The cardiac extracellular matrix (ECM) provides a platform for cells to maintain structure and function, which in turn maintains tissue function. In response to injury, the ECM undergoes remodeling that involves synthesis, incorporation, and degradation of matrix proteins, with the net outcome determined by the balance of these processes. The major goals of this review are a) to serve as an initial resource for students and investigators new to the cardiac ECM remodeling field, and b) to highlight a few of the key exciting avenues and methodologies that have recently been explored. While we focus on cardiac injury and responses of the left ventricle (LV), the mechanisms reviewed here have pathways in common with other wound healing models.

Figure 1

During the MI response, cardiac fibroblasts are recruited from resting resident cells and from a pool of circulating fibrocytes and are stimulated to undergo phenotypic modulation to become myofibroblasts. Increased proliferation and increased ECM synthesis are prime characteristics of the cardiac fibroblasts within the infarct zone. If infarct wound healing occurs optimally, the fibroblast undergoes apoptosis to decrease numbers. Persistent fibroblast activation occurs during adverse remodeling that will progress to heart failure. Abbreviations: ACE- angiotensin converting enzyme; Aldo- aldosterone; Ang II- angiotensin II; βAR- β- adrenergic receptor; bFGF- basic fibroblast growth factor; CTP- C-terminal peptide; ET-1-endothelin-1; IFNγ- Interferon γ; IL- interleukin; iNOS- inducible nitric oxide synthase; MCP-1-monocyte chemotactic protein-1; MMP- matrix metalloproteinase; ROS- reactive oxygen species; αSMA- α smooth muscle actin; TGFβ- transforming growth factor β; TIMP- tissue inhibitor of metalloproteinase; TNFα- tumor necrosis factor α; VEGF- vascular endothelial growth factor.