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学科主题: 基础医学
题名:
PGC-1 alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery
作者: Qu, Aijuan1; Jiang, Changtao1; Xu, Mingjiang1; Zhang, Yan2; Zhu, Yi1; Xu, Qingbo3; Zhang, Chenyu2; Wang, Xian1
关键词: restenosis ; antioxidants ; smooth muscle cells ; metabolic syndrome ; peroxisome proliferator-activated receptor-gamma coactivator-1 alpha
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
发表日期: 2009-09-01
DOI: 10.1152/ajpcell.00469.2008
卷: 297, 期:3, 页:C645-C653
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Physiology
研究领域[WOS]: Cell Biology ; Physiology
关键词[WOS]: KAPPA-B ACTIVATION ; MITOCHONDRIAL BIOGENESIS ; ENDOTHELIAL-CELLS ; PGC-1 COACTIVATORS ; ENERGY-METABOLISM ; OXIDATIVE STRESS ; GENE-EXPRESSION ; GROWTH ; MECHANISMS ; DISEASE
英文摘要:

Qu A, Jiang C, Xu M, Zhang Y, Zhu Y, Xu Q, Zhang C, Wang X. PGC-1 alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery. Am J Physiol Cell Physiol 297: C645-C653, 2009. First published June 24, 2009; doi:10.1152/ajpcell.00469.2008.-Oxidative stress contributes significantly to the migration of vascular smooth muscle cells (VSMCs), the major pathogenic process of vascular diseases, but the mechanism remains unclear. In the present study, we explored the role of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), a major regulator of mitochondrial biogenesis and energy balance, in VSMC migration in vitro and in vivo. Overexpression of PGC-1 alpha in cultured VSMCs led to a 74.5% reduction of migration activity and mitochondrial ROS generation by the increased expression of antioxidative proteins such as SOD-2 in the mitochondria. The knockdown of PGC-1 alpha by specific small interfering (si)RNA markedly augmented VSMC migration activity and greatly reduced mitochondrial antioxidative protein expression. Furthermore, knockdown of SOD-2 expression by siRNA greatly reversed the inhibitory effect of PGC-1 alpha overexpression on VSMC migration. In a rat carotid balloon injury model, adenovirus-mediated overexpression of PGC-1 alpha greatly reduced neointimal formation (ratio of intima to media: 0.78 +/- 0.09 vs. 1.45 +/- 0.18 in the adenovirus + green fluorescent protein gene-transfected group). Moreover, the expression of SOD-2 was significantly increased in vivo in local vessels after injury in the PGC-1 alpha-overexpressing group. These data strongly suggest that PGC-1 alpha inhibits VSMC migration and neointimal formation after vascular injury in rats, mainly by upregulating the expression of the mitochondrial antioxidant enzyme SOD-2.

语种: 英语
所属项目编号: 2006CB503802 ; 30821001 ; 307001
项目资助者: Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Repulbic of China ; Key Grant Project of Chinese Ministry of Education ; Chang Jiang Scholars Program
WOS记录号: WOS:000269584200017
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55885
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Key Lab Mol Cardiovas Sci,Minist Educ, Beijing 100191, Peoples R China
2.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Jiangsu Diabet Ctr, Nanjing 210008, Peoples R China
3.Kings Coll London, James Black Ctr, Div Cardiovasc, London WC2R 2LS, England

Recommended Citation:
Qu, Aijuan,Jiang, Changtao,Xu, Mingjiang,et al. PGC-1 alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2009,297(3):C645-C653.
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