Kistrin inhibits human smooth muscle cell interaction with fibrin.
Because of the lack of function-blocking anti-integrin antibodies that react with nonprimate species, the study of the role of integrins in in vivo animal models of atherosclerosis has been limited. In contrast, peptides or small molecules have shown less species specificity and thus may be better tools to use. In an attempt to identify integrin antagonists of potential use against smooth muscle response to injury, we investigated the role of human 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 demonstrate that Kistrin, a disintegrin that inhibits beta1, beta2, beta3, and beta5 integrin interactions, had the most potent inhibitory effect. Based on our results, Kistrin or peptides with similar pan-integrin selectivity patterns are prime candidates for use as anti-integrin antagonists in further studies of atherosclerosis and restenosis.
Yee
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KO
Department of Pathology, University of Washington, Seattle 98195, USA. kyee@caregroup.harvard.edu
Ikari
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Y
Bodary
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Schwartz
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SM
D001011:Aorta / Q000166:cytology; D001777:Blood Coagulation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D019483:Disintegrins / Q000494:pharmacology; D005337:Fibrin / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D016023:Integrins / Q000037:antagonists & inhibitors; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013454:Sulfoxides / Q000494:pharmacology
D019483:Disintegrins; D005343:Fibrinolytic Agents; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; D013454:Sulfoxides; C406822:VCAM345 peptide; C406823:penicillamyl-glycyl-arginyl-glycyl-aspartyl-seryl-prolyl-cysteinyl-alanine; C074915:G 4120; C067623:kistrin; D005337:Fibrin