Dynamic Role of Extracellular Matrix Metalloproteinases in Heart Failure

In chronic congestive heart failure, an illness affecting more than 4 million Americans, there is extensive myocardial extracellular matrix (ECM) remodeling. Failing human ventricular myocardium contains activated matrix metalloproteinases (MMPs) which are involved in adverse ECM remodeling. Our studies support the concept that impaired ECM remodeling and MMP activation are, in part, responsible for the cardiac structural deformation during heart failure. There is no known program which has declared its aim the investigation of regulation of fibrosis in hypertrophy and disruption of ECM in cardiac dilatation and failure. The development of transgenic technology, and emerging techniques for in vivo gene transfer, suggest a strategy for improving cardiac function by overexpressing or down regulation of the ECM components such as MMPs, tissue inhibitor of metalloproteinases (TIMPs), transforming growth factor β1 (TGFβ), decorin, collagen, and integrins in heart failure.