Extracellular matrix and fibroblast communication following myocardial infarction

Abstract

The extracellular matrix (ECM) provides structural support by serving as a scaffold for cells, and as such the ECM maintains normal tissue homeostasis and mediates the repair response following injury. In response to myocardial infarction (MI), ECM expression is generally upregulated in the left ventricle (LV), which regulates LV remodeling by modulating scar formation. The ECM directly affects scar formation by regulating growth factor release and cell adhesion and indirectly affects scar formation by regulating the inflammatory, angiogenic, and fibroblast responses. This review summarizes the current literature on ECM expression patterns and fibroblast mechanisms in the myocardium, focusing on the ECM response to MI. In addition, we discuss future research areas that are needed to better understand the molecular mechanisms of ECM action, both in general and as a means to optimize infarct healing.

Fig. 1

Myofibroblast numbers are markedly increased post-MI. The left panel shows smooth muscle cells localized in the vessel at baseline (day 0). The right panel shows that myofibroblasts are significantly upregulated in the non-vessel interstitium at day 7 post-MI. Nuclei are stained with DAPI (blue). Smooth muscle cells and myofibroblasts are stained with anti-α-smooth muscle actin antibody (red). This is our own unpublished result.

Fig. 2

Schematic representation of the mechanisms of ECM action in the MI setting. ECM, consisting of structural and matricellular proteins, mediates post-MI remodeling and repair by regulating scar formation, inflammation, angiogenesis, cell-ECM adhesion, growth factor production and release, and fibroblast function.