Metalloproteinases in Development and Progression of Vascular Disease

Remodeling of the vascular wall plays a role in many physiological processes, but also in the pathogenesis of major cardiovascular diseases such as restenosis and atherosclerosis. Remodeling requires proteolytic activity to degrade components of the extracellular matrix; this can be generated by the matrix metalloproteinase(MMP) system alone or in concert with the fibrinolytic (plasminogen/plasmin) system. Several lines of evidence suggest that the MMP system plays a role in vascular smooth muscle cell migration and neointima formation after vascular injury. In atherosclerotic lesions, active MMPs may contribute to plaque destabilisation by degrading extracellular matrix components, but may also promote aneurysm formation by proteolytic degradation of the elastic lamina. The MMP system may therefore represent a potential therapeutic target for treatment of restenosis or atherosclerosis.