期刊
CIRCULATION RESEARCH
卷 104, 期 7, 页码 842-850出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.108.189837
关键词
vascular smooth muscle cell; beta-lapachone; AMPK; NQO1; restenosis
资金
- Korean government [M10753020002-07N5302-00210, R0A-2006-000-10271-0, M10642140004-06N4214-0040, M10753020001-07N5302-00110, KRF-2004206-C00043]
- Brain Korea 21 Project
- National Research Foundation of Korea [R0A-2006-000-10271-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important pathogenic mechanisms in atherosclerosis and restenosis after vascular injury. In this study, we investigated the effects of beta-lapachone (beta L) (3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione), which is a potent antitumor agent that stimulates NAD(P)H:quinone oxidoreductase (NQO)1 activity, on neointimal formation in animals given vascular injury and on the proliferation of VSMCs cultured in vitro. beta L significantly reduced the neointimal formation induced by balloon injury. beta L also dose-dependently inhibited the FCS- or platelet-derived growth factor-induced proliferation of VSMCs by inhibiting G(1)/S phase transition. beta L increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 in rat and human VSMCs. Chemical inhibitors of AMPK or dominant-negative AMPK blocked the beta L-induced suppression of cell proliferation and the G(1) cell cycle arrest, in vitro and in vivo. The activation of AMPK in VSMCs by beta L is mediated by LKB1 in the presence of NQO1. Taken together, these results show that beta L inhibits VSMCs proliferation via the NQO1 and LKB1-dependent activation of AMPK. These observations provide the molecular basis that pharmacological stimulation of NQO1 activity is a new therapy for the treatment of vascular restenosis and/or atherosclerosis which are caused by proliferation of VSMCs. (Circ Res. 2009;104:842-850.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据