INTEGRINS AND CARDIOVASCULAR-DISEASE

Cardiovascular diseases involve abnormal cell-cell interactions leadin g to the development of atherosclerotic plaque, which when ruptured ca uses massive platelet activation and thrombus formation. Parts of a lo ose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell recept ors interacting with adhesive proteins or with counterreceptors on oth er cells. There is now solid evidence that the major integrin on plate lets, the fibrinogen receptor alpha(IIb)beta(3) has an important role in several aspects of cardiovascular diseases and that its regulaled i nhibition leads to a reduction in incidence and mortality due to these disorders. The development of alpha(IIb)beta(3) inhibitors is an impo rtant strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prop hylaxis of these conditions. Although all the associated problems have not been solved. the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated furt her research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit gene s ablated have contributed to a better understanding of the function o f integrins in development of the cardiovascular system.