Cardiac muscle is unique because it contracts ceaselessly throughout the life and is highly resistant to
fatigue. The marvelous nature of the cardiac muscle is attributed to its matrix that maintains structural and functional integrity and provides ambient micro-environment required for mechanical, cellular and molecular activities in the heart. Cardiac matrix dictates the endothelium myocyte (EM) coupling and contractility of cardiomyocytes. The
matrix metalloproteinases (
MMPs) and their
tissue inhibitor of metalloproteinases (TIMPs) regulate matrix degradation that determines cardiac
fibrosis and myocardial performance. We have shown that MMP-9 regulates differential expression of micro RNAs (
miRNAs),
calcium cycling and contractility of cardiomyocytes. The differential expression of
miRNAs is associated with angiogenesis,
hypertrophy and
fibrosis in the heart. MMP-9, which is involved in the degradation of cardiac matrix and induction of
fibrosis, is also implicated in inhibition of survival and differentiation of cardiac stem cells (CSC). Cardiac matrix is distinct because it renders mechanical properties and provides a framework essential for differentiation of cardiac progenitor cells (
CPC) into specific lineage. Cardiac matrix regulates myocyte contractility by EM coupling and
calcium transients and also directs
miRNAs required for precise regulation of continuous and synchronized beating of cardiomyocytes that is indispensible for survival. Alteration in the matrix homeostasis due to induction of
MMPs, altered expression of specific
miRNAs or impaired signaling for contractility of cardiomyocytes leads to catastrophic effects. This review describes the mechanisms by which cardiac matrix regulates myocardial performance and suggests future directions for the development of treatment strategies in
cardiovascular diseases.