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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAQA2IQrjwxnOb2yEhZZeBPBUHd9lH8XyG38gDEbvgrac#_5 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAQA2IQrjwxnOb2yEhZZeBPBUHd9lH8XyG38gDEbvgrac#_3 http://purl.org/dc/elements/1.1/identifier AHA Abstracts 1496 http://www.tkuhn.ch/bel2nanopub/RAQA2IQrjwxnOb2yEhZZeBPBUHd9lH8XyG38gDEbvgrac#_3 http://purl.org/dc/elements/1.1/title AHA Abstracts 1496 http://www.tkuhn.ch/bel2nanopub/RAQA2IQrjwxnOb2yEhZZeBPBUHd9lH8XyG38gDEbvgrac#_3 http://purl.org/dc/elements/1.1/type Other http://www.tkuhn.ch/bel2nanopub/RAQA2IQrjwxnOb2yEhZZeBPBUHd9lH8XyG38gDEbvgrac#_4 http://www.w3.org/ns/prov#value HMG-CoA reductase inhibitors have direct vascular effects that contribute to plaque stability. In the present study we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and pravastatin augment the adhesion of human (HSMCs) and rat aortic smooth muscle cells (RASMCs) to collagen I via induction of alpha2beta1-integrin receptors. Atorvastatin (0.1 mcrM) increased the adhesion of HSMCs to collagen I up to 2-fold (p<0.01) and pravastatin (1.0 mcrM) up to 1.8-fold (p<0.01) after treatment for at least 24 hours. This increase in adhesion was concentration-dependent and was observed for treatment periods from 16 to 72 hours. Inhibition of isoprenoid synthesis with mevalonate and geranyl-geraniol prevented the statin-induced effect on human and rat smooth muscle cells. Flow cytometry revealed an increased expression of alpha2- and beta1-integrins after treatment with atorvastatin (0.1 mcrM) at 24 and 48 hours. Atorvastatin increased levels of b1-integrin mRNA after 12 and 24 hours treatment in HSMCs, which was inhibited by mevalonate. Furthermore, atorvastatin (0.1 mcrM) and pravastatin (1.0 mcrM) inhibited chemotaxis of HSMCs on collagen I, which was also reversed by mevalonate treatment. In contrast, inhibition of b1-integrins with a specific antibody nearly doubled (p<0.01) the rate of chemotaxis. These data indicate that the chemotactic activity in HSMCs is inhibited in part by upregulation of alpha2beta1-integrin receptors. 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