Integrins and cardiovascular disease.
Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor alpha IIb beta 3, has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of alpha IIb beta 3 inhibitors is an important 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 prophylaxis 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 further 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 genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system.
Clemetson
K J
KJ
Theodor Kocher Institute, University of Berne, Switzerland. clemetson@tki.unibe.ch
Clemetson
J M
JM
D001161:Arteriosclerosis / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000502:physiology; D013927:Thrombosis / Q000378:metabolism
D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex