Tetrahydrobiopterin Inhibits PDGF-stimulated Migration and Proliferation in Rat Aortic Smooth Muscle Cells via the Nitric Oxide Synthase-independent Pathway.
10.4196/kjpp.2010.14.3.177
- Author:
Xiaowen JIANG
1
;
Bokyung KIM
;
Haiyue LIN
;
Chang Kwon LEE
;
Junghwan KIM
;
Hyun KANG
;
Pilyoung LEE
;
Seung Hyo JUNG
;
Hwan Myung LEE
;
Kyung Jong WON
Author Information
1. Department of Physiology and Biotechnology, Konkuk University, Chungju 380-701, Korea. kjwon@kku.ac.kr
- Publication Type:Original Article
- Keywords:
Tetrahydrobiopterin;
Migration;
Nitric oxide;
Proliferation;
Rat aortic smooth muscle cells
- MeSH:
Animals;
Atherosclerosis;
Biopterin;
Bromodeoxyuridine;
Cell Movement;
Cell Survival;
Muscle, Smooth;
Muscle, Smooth, Vascular;
Myocytes, Smooth Muscle;
Nitric Oxide;
Nitric Oxide Synthase;
Proto-Oncogene Proteins c-sis;
Rats;
Superoxides;
Vascular Diseases
- From:The Korean Journal of Physiology and Pharmacology
2010;14(3):177-183
- CountryRepublic of Korea
- Language:English
-
Abstract:
Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BB-induced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with N G-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.
