title: The induction of yes-associated protein expression after arterial injury is crucial for smooth muscle phenotypic modulation and neointima formation.
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.
  
  
  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.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Gao
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Erin Yund
authors.initials: EY
authors.lastname: Harmon
authors.forename: Xu
authors.initials: X
authors.lastname: Zhi
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Lennartz
authors.forename: Margarida
authors.initials: M
authors.lastname: Barroso
authors.forename: Mohamed
authors.initials: M
authors.lastname: Trebak
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
authors.forename: Jiliang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002339:Carotid Arteries / Q000201:enzymology / Q000473:pathology; D020212:Carotid Artery Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D018797:Cell Cycle Proteins; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D058426:Neointima; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection; D057772:Vascular System Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C509425:Yap1 protein, rat