Statins Inhibited the ADP-Stimulated Activation of Integrins alpha v beta5 and alpha v beta3 of Vascular Smooth Muscle Cells.
10.4070/kcj.2006.36.12.809
- Author:
Seung Jae JOO
1
;
Soo Chang LEE
;
Jae Woo LEE
Author Information
1. Department of Internal Medicine, Cheju National University Hospital, Jeju, Korea. sejjoo@cheju.ac.kr
- Publication Type:Original Article
- Keywords:
Adenosine diphosphate;
Integrins;
Myocytes, smooth muscle
- MeSH:
Adenosine Diphosphate;
Flow Cytometry;
Humans;
Hydroxymethylglutaryl-CoA Reductase Inhibitors*;
Integrin alpha Chains;
Integrin alphaV;
Integrins*;
Muscle, Smooth, Vascular*;
Myocytes, Smooth Muscle;
Prothrombin;
Simvastatin
- From:Korean Circulation Journal
2006;36(12):809-816
- CountryRepublic of Korea
- Language:Korean
-
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 alpha v beta5 and alpha v beta3 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, alpha v beta5 and alpha v beta3. The ADP-stimulated adhesion was partially prevented by LM609, which blocked integrin alpha v beta3 (13% inhibition), and markedly prevented by P1F5, which blocked integrin alpha v beta5 (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, alpha v beta5 and alpha v beta3, but did inhibit the ADP-stimulated activation of the integrins of HASMC.
