Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1.
10.4196/kjpp.2011.15.4.203
- Author:
Jung Eun KIM
1
;
Jin Young SUNG
;
Chang Hoon WOO
;
Young Jin KANG
;
Kwang Youn LEE
;
Hee Sun KIM
;
Woo Hyung KWUN
;
Hyoung Chul CHOI
Author Information
1. Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. hcchoi@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Cilostazol;
Proliferation;
ROS;
AMPK;
HO-1
- MeSH:
AMP-Activated Protein Kinases;
Cell Proliferation;
Cyclic AMP-Dependent Protein Kinases;
Heme;
Heme Oxygenase-1;
Muscle, Smooth, Vascular;
Phosphorylation;
Platelet-Derived Growth Factor;
Reactive Oxygen Species;
Tetrazoles
- From:The Korean Journal of Physiology and Pharmacology
2011;15(4):203-210
- CountryRepublic of Korea
- Language:English
-
Abstract:
Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. We investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose- and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.
