Korean J Physiol Pharmacol.
2011 Aug;15(4):203-210. 10.4196/kjpp.2011.15.4.203.
Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1
- Affiliations
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- 1Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. hcchoi@med.yu.ac.kr
- 2Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- 3Department of Microbiology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- 4Department of Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- KMID: 1448925
- DOI: http://doi.org/10.4196/kjpp.2011.15.4.203
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.
Keyword
MeSH Terms
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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
AMP-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Heme
Heme Oxygenase-1
Platelet-Derived Growth Factor
Reactive Oxygen Species
Tetrazoles
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