Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis.
This study determines the effect of hepatocyte growth factor (HGF) on post-infarction left ventricular (LV) remodeling and cardiac function. In mice, on day 1 after myocardial infarction (MI), HGF (0.45 mg/kg per day) was injected into the tail vein for 7 days (n = 12). In the control mice (n = 12), 0.9% sodium chloride was injected instead of HGF. Hemodynamic data were obtained in vehicle treated control and HGF-treated hearts 4 weeks after the onset of MI. In the HGF-treated group, cardiac function was well preserved as indicated by LV pressure-volume relationship. These mice exhibited better LV systolic and diastolic function. The infarcted LV wall in HGF-treated heart was thicker as compared to vehicle treated group. Fibrosis and infarct size of the ventricular wall was significantly reduced in the HGF-treated hearts. 5-Bromo-2'-deoxy-uridine (BrdU) and Ki67 positive cardiomyocytes were observed in the border area of the HGF-treated infarcted hearts. c-Met and c-kit positive cardiomyocytes were observed in the border area and epicardium. Angiogenesis was significantly enhanced in HGF-treated hearts as determined by vessel density per unit area. A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation. Treatment with HGF improved heart function through angiogenesis, ventricular wall thickening, and hypertrophy of cardiomyocytes. The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway.
Wang
Yigang
Y
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
Ahmad
Nauman
N
Wani
Maqsood A
MA
Ashraf
Muhammad
M
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000276:immunology; D005355:Fibrosis; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D018952:Antigens, CD34; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D017228:Hepatocyte Growth Factor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt