Myocardial remodelling and matrix metalloproteinases in heart failure: turmoil within the interstitium.

ABSTRACT

The progression of left ventricular (LV) dysfunction is often accompanied by changes in LV geometry and myocardial architecture that can be defined as LV myocardial remodelling. An important event in LV myocardial remodelling is alterations in the extracellular matrix (ECM). A family of zinc-dependent proteases implicated in facilitating myocardial tissue remodelling by degrading components of the ECM are the matrix metalloproteinases (MMPs). The temporal expression of MMPs and the local tissue inhibitors of MMPs (TIMPs) appear to be differentially regulated in several cardiovascular disease states such as myocardial infarction, LV hypertrophy, and dilated cardiomyopathy. Both pharmacological and genetic modulation of myocardial MMP expression has been demonstrated to alter the course of LV myocardial remodelling and LV dysfunction. The induction of MMPs within the myocardium during the heart failure process probably results in liberation of bioactive molecules, proteolytic degradation of ECM structural proteins, and alterations in cell-cell contact and adhesion. Modifying MMP expression and activation may reduce this turmoil within the myocardial interstitium and, in turn, prove to be a useful therapeutic paradigm for heart failure treatment.