Controlling myocardial matrix remodeling: implications for heart failure

Progressive congestive heart failure (CHF) is often accompanied by a change in left ventricular geometry and myocardial architecture, commonly referred to as myocardial remodeling. It has been observed that important changes occur within the collagen matrix of the myocardium, potentially contributing to the remodeling process. The myocardial collagen matrix is influenced by 2 fundamental processes: collagen synthesis and collagen degradation. Matrix metalloproteinases are an endogenous family of zinc-dependent enzymes involved in matrix degradation and have been shown to be regulated by a class of proteins called the tissue inhibitors of metalloproteinases. Several studies have identified changes in myocardial matrix metalloproteinase and tissue inhibitors of metalloproteinase expression with the development of CHF. These observations have led to the hypothesis that increased metalloproteinase activity and decreased levels of tissue inhibitors of metalloproteinase result in collagen remodeling that disrupts myocyte alignment and facilitates the left ventricular remodeling process with CHF. Thus, the development of pharmacologic agents that will modulate the activity and expression of myocardial matrix metalloproteinases represents a new and potentially significant therapeutic target for developing CHF.