Myocardial remodeling: The role of matrix metalloproteinases

The activation of metalloproteinases (MMPs), enzymes destroying extracellul ar matrix, presents the initial step of myocardial remodeling during adapti ve responses of the heart to changes of functional load or action of drugs. This is usually combined with reduction of activity of tissue inhibitors o f MMPs and brings about a destruction:of some collagen links with further i ncreased synthesis of collagen of III and I types. The damage of cardiomyoc ytes under the influence of ischemia-reperfusion, or adriamycin, or high do se catecholamines is associated with significant alteration of collagen net work. The participation of oxygen free radicals in this process has been sh own. A prolonged predominance of the activity of MMPs over their inhibitors , combined with regional destruction of the network, creates the basis for the development of fibrosis accompanying ischemic or dilative cardiomyopath y.