Korean Circ J.  2004 May;34(5):500-506. 10.4070/kcj.2004.34.5.500.

The Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells and Expression of iNOS and p21

• Lee KJ
• Yun SW
• Kim SW
• Kim TH
• Kim CJ
• Ryu WS

• KMID: 1769249
• DOI: http://doi.org/10.4070/kcj.2004.34.5.500

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.

Keyword

Cilostazol; Nitric-oxide synthase; Protein p21; Vascular smooth muscle

MeSH Terms

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
Cyclic AMP
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Platelet-Derived Growth Factor