Integrins and cardiovascular disease

Abstract

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.

Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum

“…Alterations to integrin function and/or expression is a common step in inflammation and cardiovascular disease (Clemetson and Clemetson, 1998;Hynes, 2002), and promote anchorageindependent growth, invasion and metastasis in cancer cells (Guo and Giancotti, 2004;Hood and Cheresh, 2002;Schwartz, 1997). Integrins respond to cytoplasmic signals through changes in integrinligand affinity, termed 'inside-out' signalling.…”

Charakterisierung molekularer Mechanismen der anti-angiogenen Aktivität von GBP-1 in Endothelzellen

“…Integrine sind weit verbreitete Transmembranrezeptoren, die auf vielen unterschiedlichen Zelltypen, wie EZ, GMZ, Monozyten, Leukozyten und Thrombozyten, exprimiert werden (Clemetson and Clemetson, 1998). Von den 24 bekannten Integrinen spielen 16 eine bedeutende Rolle in der vaskulären Biologie, wobei acht dieser Integrine von EZ selbst exprimiert werden (Rupp and Little, 2001).…”

“…Von den 24 bekannten Integrinen spielen 16 eine bedeutende Rolle in der vaskulären Biologie, wobei acht dieser Integrine von EZ selbst exprimiert werden (Rupp and Little, 2001). Hierzu zählen die Integrine α v β 3 , α 2 β 1 , α 3 β 1 und α 5 β 1 (Luscinskas and Lawler, 1994), aber auch α 1 β 1 , α 6 β 1, α 4 β 1 und α v β 5 (Brezinschek et al, 1996;Clemetson and Clemetson, 1998;Rupp and Little, 2001 Bei der Migration bildet die Zelle in Migrationsrichtung eine Aktin-reiche Vorderseite und eine Aktin-arme Rückseite aus (Abb. 5).…”

Vimocin and Vidapin, Cyclic KTS Peptides, Are Dual Antagonists ofα1β1/α2β1Integrins with Antiangiogenic Activity

“…Studies with a 1 /a 2 integrin A domain chimeras confirmed a preference for different collagen types (Abair et al, 2008). As such, integrin receptors are central to the etiology and pathology of many diseases, such as cardiovascular (Clemetson and Clemetson, 1998), inflammatory (Apostolaki et al, 2008) and neurodegenerative disorders (Engelhardt and Kappos, 2008). They therefore have been actively targeted for drug discovery.…”