Kistrin inhibits human smooth muscle cell interaction with fibrin

Because of the lack of function-blocking anti-integrin antibodies that reac t with nonprimate species, the study of the role of integrins in in vivo an imal models of atherosclerosis has been limited. In contrast, peptides or s mall molecules have shown less species specificity and thus may be better t ools to use. In an attempt to identify integrin antagonists of potential us e against smooth muscle response to injury, we investigated the role of hum an smooth muscle cell interactions with fibrin by using a panel of integrin antagonists consisting of the snake venom disintegrin, Kistrin, as well as cyclic peptides with well-defined integrin antagonists activities. We demo nstrate that Kistrin, a disintegrin that inhibits beta 1, beta 2, beta 3, a nd beta 5 integrin interactions, had the most potent inhibitory effect. Bas ed on our results, Kistrin or peptides with similar pan-integrin selectivit y patterns are prime candidates for use as anti-integrin antagonists in fur ther studies of atherosclerosis and restenosis. (C) 2000 Elsevier Science L td. All rights reserved.