The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation
Wang XB1; Hu GQ1; Gao XW3; Wang YM1; Zhang W1; Harmon EY2; Zhi X2; Xu ZP3; Lennartz MR2; Barroso M1
刊名ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
2012
卷号32期号:11页码:2662-+
关键词yes-associated protein smooth muscle phenotypic modulation neointima formation
通讯作者zhouj1@mail.amc.edu
英文摘要Objective-Abnormal proliferation and migration of vascular smooth muscle cells (SMCs) are the key events in the progression of neointima formation in response to vascular injury. The goal of this study is to investigate the functional role of a potent oncogene yes-associated protein (YAP) in SM phenotypic modulation in vitro and in vivo. 

Methods and Results-In vitro cell culture and in vivo in both mouse and rat arterial injury models YAP expression is significantly induced and correlated with the vascular SMC synthetic phenotype. Overexpression of YAP promotes SMC migration and proliferation while attenuating SM contractile gene expression. Conversely, knocking down endogenous YAP in SMCs upregulates SM gene expression but attenuates SMC proliferation and migration. Consistent with this, knocking down YAP expression in a rat carotid balloon injury model and genetic deletion of YAP, specifically, in vascular SMCs in mouse after carotid artery ligation injury attenuates injury-induced SM phenotypic switch and neointima formation. 

Conclusion-YAP plays a novel integrative role in SM phenotypic modulation by inhibiting SM-specific gene expression while promoting SM proliferation and migration in vitro and in vivo. Blocking the induction of YAP would be a potential therapeutic approach for ameliorating vascular occlusive diseases. (Arterioscler Thromb Vasc Biol. 2012;32:2662-2669.)
收录类别SCI
资助信息The project described was supported by a grant (1R01HL109605- 01A1) from the National Heart, Lung, and Blood Institute, National Institutes of Health to J. Zhou and a Postdoctoral Fellowship from American Heart Association to X. Wang.
语种英语
WOS记录号WOS:000310058900020
公开日期2013-04-10
内容类型期刊论文
源URL[http://159.226.149.42:8088/handle/152453/7331]  
专题昆明动物研究所_肿瘤生物学
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位1.Center for Cardiovascular Sciences,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
2.Center for Cell Biology and Cancer Research,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
3.Albany Medical College, Albany, NY; Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
4.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
推荐引用方式
GB/T 7714
Wang XB,Hu GQ,Gao XW,et al. The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2012,32(11):2662-+.
APA Wang XB.,Hu GQ.,Gao XW.,Wang YM.,Zhang W.,...&Zhou JL[*].(2012).The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,32(11),2662-+.
MLA Wang XB,et al."The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 32.11(2012):2662-+.
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