Matrix metalloproteinases and coronary artery disease: a novel therapeutic target

Matrix metalloproteinases (MMP) are a family of enzymes that selectively digest individual components of the extracellular matrix. Their function has been studied in both normal physiologic processes and pathologic states. In the blood vessel, MMPs play an important role in maintaining the vessel's integrity by breaking down extracellular matrix while new matrix is being synthesized. This is necessary to avoid weakening from continuous mechanical stresses. However, in certain environments, these MMPs may contribute to cardiovascular pathologic processes. The purpose of this review is to first discuss the role of MMPs in coronary vascular disease. Evidence suggests that MMPs contribute to the development of de novo atherosclerotic plaques and postangioplasty restenotic plaques by allowing smooth muscle cells to migrate from the vascular media to the intima. Evidence also suggests that MMPs contribute to the rupture of these plaques by degrading the fibrous cap that surrounds them. With this increased molecular information that concerns the pathogenesis of coronary vascular disease, new molecular therapies aimed at altering these processes are being investigated. The rationale, mode of delivery, and prospects for success of these therapies will also be discussed here.