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The induction of yes-associated protein expression after arterial injury is crucial for smooth muscle phenotypic modulation and neointima formation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wang, Xiaobo Hu, Guoqing Gao, Xiangwei Wang, Yong Zhang, Wei Harmon, Erin Yund Zhi, Xu Bo Xu, Zhengping Lennartz, Michelle R. Barroso, Margarida Trebak, Mohamed Chen, Ceshi Zhou, Jiliang |
| Copyright Year | 2012 |
| Abstract | 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. CONCLUSIONS 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. |
| Starting Page | 26 |
| Ending Page | 33 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2012/08/23/ATVBAHA.112.254730.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/32/11/2662.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2012/08/23/ATVBAHA.112.254730.full.pdf |
| PubMed reference number | 22922963v1 |
| Alternate Webpage(s) | https://doi.org/10.1161/ATVBAHA.112.254730 |
| DOI | 10.1161/ATVBAHA.112.254730 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume Number | 32 |
| Issue Number | 11 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Carotid Arteries Cell Culture Techniques Deletion Mutation Gene Expression Inhibition Ligation Muscle, Smooth, Vascular Myocytes, Smooth Muscle Neointima Oncogenes Peripheral Vascular Diseases Promotion (action) Smooth muscle (tissue) Streptomycin Vascular System Injuries protein expression |
| Content Type | Text |
| Resource Type | Article |