Statins Inhibited the ADP-Stimulated Activation of Integrins αvβ5and αvβ3of Vascular Smooth Muscle Cells

Abstract

Background and Objectives：Integrins mediate the migration, adhesion and proliferation of vascular smooth muscle cells. Adenosine diphosphate (ADP) can activate vascular integrins. We assessed the hypothesis that ‘statins inhibit the ADP-stimulated activation of integrins αvβ5 and αvβ3 in human aortic smooth muscle cells (HASMC)’. Materials and Methods：The expressions of integrins were analyzed using flow cytometry. The activations of integrins were evaluated using the adhesion assay, with prothrombin as an activation-dependent ligand. The MTT assay was used to evaluate the proliferation. Results：Statins did not suppress the expressions of the integrins, αvβ5 and αvβ3. The ADP-stimulated adhesion was partially prevented by LM609, which blocked integrin αvβ3 (13% inhibition), and markedly prevented by P1F5, which blocked integrin αvβ5 (76% inhibition; n=5, p<0.05). However, the proliferation was inhibited by c7E3 and LM609, but not by P1F5. Statins inhibited the ADP-stimulated adhesions in a dose-dependent manner after 15 min of pretreatment. After incubating HASMC with statins for 1 day, simvastatin and fluvastatin inhibited the adhesion by 70 and 66%, respectively (n=5, p<0.05 vs. no statin). Statins also inhibited the ADP-stimulated proliferation of HASMC. Conclusion：Statins did not suppress the expressions of the integrins, αvβ5 and αvβ3, but did inhibit the ADP-stimulated activation of the integrins of HASMC. (Korean Circulation J 2006; 36:809-816)