The Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells and Expression of iNOS and p21.
10.4070/kcj.2004.34.5.500
- Author:
Kwang Je LEE
1
;
Sin Weon YUN
;
Sang Wook KIM
;
Tae Ho KIM
;
Chee Jeong KIM
;
Wang Seong RYU
Author Information
1. Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Cilostazol;
Nitric-oxide synthase;
Protein p21;
Vascular smooth muscle
- MeSH:
Adipocytes;
Angioplasty;
Animals;
Blotting, Western;
Cell Count;
Cell Proliferation;
Cyclic AMP;
Humans;
Muscle, Smooth, Vascular*;
Myocytes, Cardiac;
NG-Nitroarginine Methyl Ester;
Nitric Oxide Synthase;
Nitric Oxide Synthase Type II;
Percutaneous Coronary Intervention;
Platelet-Derived Growth Factor
- From:Korean Circulation Journal
2004;34(5):500-506
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND AND OBJECTIVES: Cilostazol is an anti-platelet and arterial vasodilating drug that inhibits phosphodiesterase type III, an enzyme that breaks down cyclic AMP in platelets, vascular smooth muscle cells, cardiac myocytes and adipocytes. Several animal and human studies have shown that cilostazol has the potential to reduce restenosis after coronary angioplasty, but the precise mechanism by which the inhibition of vascular smooth muscle cell growth occurs from an increase in cyclic AMP is not yet clear. MATERIALS AND METHODS: We investigated the effects of cilostazol on cell proliferation and expression of iNOS and p21 by western blotting with the cultured aortic vascular smooth muscle cells stimulated with platelet-derived growth factor BB. RESULTS: In comparison to the control, treatment with cilostazol significantly inhibited (p<0.05) the increase in cell number. Inducible nitric oxide synthase (iNOS) and p21 expression increased with cilostazol treatment, and these effects of cilostazol were eliminated by simultaneous incubation with the NOS inhibitor, L-NAME. These results indicate that cilostazol increases p21 expression at least partially through an iNOS-dependent pathway in cultured vascular smooth muscle cells stimulated with PDGF-BB. CONCLUSION: These findings suggest that cilostazol has a direct inhibitory effect on abnormal proliferation of vascular smooth muscle cells accompanied by the induction of iNOS-dependent p21 expression, and cilostazol may have potential to prevent restenosis after percutaneous coronary intervention by this mechanism.
