title: GHSR-1a is a novel pro-angiogenic and anti-remodeling target in rats after myocardial infarction.
abstract: Cardiac remodeling and subsequent heart failure is an increasing public health problem after myocardial infarction (MI). The aim of our research is to investigate whether gene therapy of growth hormone secretagogue receptor 1a may regulate cardiac remodeling and function after MI. Adenoviral vector expressing GHSR-1a or empty adeno-null was injected into rat peri-infarct myocardium after left anterior descending coronary artery ligation. GHSR-1a expression was confirmed by western blotting. 14 days after operation, haemodynamic and echocardiographic analysis demonstrated that GHSR-1a treatment significantly improved survive rate, increased scar thickness, preserved LV diameter, restored cardiac function and increased angiogenesis. There was no difference in infarct size between MI+Ad-GHSR-1a group and MI + Ad-null group. Additionally, increased protein expression of Akt phosphorylation and AMP-activated protein kinase phosphorylation in the infarct border myocardium were also observed. Moreover, GHSR-1a overexpression significantly enhanced tube formation in human umbilical endothelial cells (HUVECs) under ischemia condition. Knockdown of GHSR-1a by siRNA markedly decreased vascular endothelial growth factor expression as well as mRNA levels of Akt and AMPK. In conclusion, GHSR-1a gene therapy improves cardiac remodeling and function in rats after myocardial infarction. This may be a new anti-remodeling target to MI.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Jiefang Road 238, Wuchang, 430060 Wuhan, PR China. Electronic address: yuanmingjie8341@163.com.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Yuan
authors.affiliation: Cardiovascular Research Center, University of Virginia, MR5 building, Room 1332, 415 Lane RD, Charlottesville, VA 22908, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Jiefang Road 238, Wuchang, 430060 Wuhan, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Jiefang Road 238, Wuchang, 430060 Wuhan, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Jiefang Road 238, Wuchang, 430060 Wuhan, PR China.
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
authors.affiliation: Cardiovascular Research Center, University of Virginia, MR5 building, Room 1332, 415 Lane RD, Charlottesville, VA 22908, United States.
authors.forename: Danny
authors.initials: D
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D054440:Receptors, Ghrelin; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases
keywords: Angiogenesis; Cardiac remodeling; GHSR-1a; Myocardial infarction