title: CHIP enhances angiogenesis and restores cardiac function after infarction in transgenic mice.
abstract: BACKGROUND
  Carboxyl terminus of Hsp70-interacting protein (CHIP) is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis. However, the effect of CHIP on angiogenesis, cardiac function and survival 4 weeks after myocardial infarction (MI) remain to be explored.
  
  
  METHODS
  Wild-type (WT) and transgenic mice (TG) with cardiac-specific overexpression of CHIP were used for coronary artery ligation. The cardiac function, cardiomyocyte apoptosis, inflammation and angiogenesis were examined by echocardiography, histological analysis, real-time PCR and Western blot analysis.
  
  
  RESULTS
  At 4 weeks of after coronary artery ligation, echocardiography demonstrated that cardiac remodeling and dysfunction were prevented in TG mice compared with WT mice. The infarct size, cardiomyocyte apoptosis and inflammation were significantly reduced in TG mice than in WT mice. The survival rate after MI in TG mice was higher than that of WT mice. Furthermore, the levels of p53 protein was markedly decreased, but the expression of HIF-1α and VEGF, and the formation of capillary and arteriole after MI were significantly enhanced in TG mice compared with WT mice.
  
  
  CONCLUSIONS
  We report the first in vivo evidence that CHIP enhances angiogenesis, inhibits inflammation, restores cardiac function, and improves survival at 4 weeks after MI. The present study expands on previous results and defines a novel mechanism. Thus, increased CHIP level may provide a novel therapeutic approach for left ventricular dysfunction after MI.
authors.affiliation: Department of Laboratory Medicine, the Second Hospital of Shandong University, Jinan, China. Xuchengwei-jyk@163.com
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Xu
authors.forename: Tian-Peng
authors.initials: TP
authors.lastname: Zhang
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C492951:Stub1 protein, mouse; D044767:Ubiquitin-Protein Ligases