Korean Circ J.  2006 Dec;36(12):809-816. 10.4070/kcj.2006.36.12.809.

Statins Inhibited the ADP-Stimulated Activation of Integrins alpha v beta5 and alpha v beta3 of Vascular Smooth Muscle Cells

• Joo SJ
• Lee SC
• Lee JW

• KMID: 2013164
• DOI: http://doi.org/10.4070/kcj.2006.36.12.809

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.

Keyword

Adenosine diphosphate; Integrins; Myocytes, smooth muscle

MeSH Terms

Adenosine Diphosphate
Flow Cytometry
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Integrin alpha Chains
Integrin alphaV
Integrins*
Muscle, Smooth, Vascular*
Myocytes, Smooth Muscle
Prothrombin
Simvastatin
Adenosine Diphosphate
Integrin alpha Chains
Integrin alphaV
Integrins
Prothrombin
Simvastatin