Background; Integrins mediate the migration, adhesion and proliferation of vascular smooth muscle cells, and ADP can activate vascular integrins. We assessed the hypothesis that HMG CoA reductase inhibitors, statins, inhibit the ADP-stimulated activation of integrins αvβ5 and αvβ3 in human aortic smooth muscle cells (HASMC). Methods; The expressions of integrins αvβ3 and αvβ5 on HASMC were analyzed by flow cytometry. Activations of integrins αvβ3 and αvβ5 were evaluated by the adhesion assay using prothrombin as an activation-dependent ligand. The MTT assay was used to evaluate the proliferation of HASMC. Results; Simvastatin and fluvastatin (5 μM) did not suppress the expressions of integrins αvβ3 and αvβ5 of HASMC after 1 day- co-culture. HASMC had more integrin αvβ5 than αvβ3. ADP increased the adhesion of HASMC to prothrombin and the proliferation in a dose-dependent manner, resulting in the maximal adhesion and proliferation at 100 μM. The adhesion was prevented partially by LM609, which blocks integrin αvβ3 (13% inhibition) and markedly by P1F5, which blocks integrin αvβ5 (76% inhibition; n=5, p<0.05). However, the proliferation was inhibited by c7E3 and LM609 (88%; n=4, p<0.05), but not by P1F5. Simvastatin and fluvastatin inhibited the ADP-stimulated adhesions of HASMC in a dose-dependent manner (at 10 μM, 15% and 27% inhibition; at 100 μM, 45% and 72% inhibition, respectively; n=5, p<0.05) after 15 min pretreatment. After incubating HASMC with statins at the concentration of 5 μM for 1 day, simvastatin and fluvastatin inhibited the adhesion by 70% and 66%, respectively (n=5, p<0.05 vs. no statin). Simvastatin and fluvastatin inhibited the ADP-stimulated proliferation of HASMC in a dose-dependent manner (at 10 μM, 18% and 10% inhibition; at 100 μM, 53% and 23% inhibition, respectively; n=6, p<0.05). Conclusions; ADP activated integrins αvβ5 and αvβ3 of HASMC. Simvastatin and fluvastatin did not suppress the expression of integrins αvβ5 and αvβ3, but inhibited the activation of these integrins. The adhesion of HASMC to prothrombin appeared to be mediated mainly by integrin αvβ5, and the proliferation by αvβ3.
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