Role Of Metalloproteinases in Plaque Rupture

SUMMARYRupture of the fibrous cap over an atherosclerotic plaque is the main cause of myocardial infarctions and strokes. Plaques vulnerable to rupture have a relatively thin fibrous cap, are highly inflamed and contain less structural collagen. This suggests that increased production of proteases, including metalloproteinases (MMPs), in response to inflammation is responsible for weakening the plaque cap. If so, then MMPs or the inflammatory mediators that lead to their overexpression are attractive targets for plaque stabilizing therapy. On the other hand, remodeling of extracellular matrix and cell surface proteins promotes migration and proliferation of endothelial and smooth muscle cells which could promote vascular repair and therefore plaque stability. Greater understanding of the role of individual MMPs and the regulation of their production is therefore needed to refine therapeutic approaches.