Matrix metalloproteinases and cardiovascular disease.

Matrix metalloproteinases (MMPs) are a group of endopeptidases with capacity to cleave components of extracellular matrix, such as collagen and elastin. The ability to modify the tissues is important for several aspects of normal and abnormal physiology. Approximately 20 different MMPs are identified, and they can be subdivided into different groups according to which components of the extracellular matrix they degrade. MMPs are secreted in a latent proform and require activation for proteolytic activity. The activity of MMPs is normally low in healthy tissue, but the increased expression and activity of several MMPs in a range of pathological processes, such as inflammation and ventricular remodelling after myocardial infarction, might indicate that they play a role in the pathophysiology and progression of atherosclerotic disease. The activity of MMPs is tightly regulated at gene transcription level and is also regulated by their secretion in an inactive zymogen form that requires extracellular activation and co-secretion of the tissue inhibitors of metalloproteinases (TIMPs). In healthy humans, MMP-2 and the inhibitory TIMP-1 and TIMP-2 are expressed across the vessel wall. Furthermore, focally increased expression of several MMPs and presence of MMP activity have been observed in diseased human arteries and in association with arterial morphologicalchanges in experimental models of atherosclerosis. MMPs may influence the process of atherosclerotic lesion formation in different ways. MMP activity may contribute to the pathogenesis of atherosclerosis by facilitating migration of vascular smooth muscle cells through the internal elastic lamina into the intima of the vessel wall, where they proliferate and contribute to plaque formation. However, MMP activity may also diminish plaque volume by degrading extracellular matrix in the intima. Mechanisms