Wang Yigang, Ahmad Nauman, Wani Maqsood A, Ashraf Muhammad
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
J Mol Cell Cardiol. 2004 Nov;37(5):1041-52. doi: 10.1016/j.yjmcc.2004.09.004.
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.
本研究确定肝细胞生长因子（HGF）对心肌梗死后左心室（LV）重构和心脏功能的影响。在小鼠中，于心肌梗死（MI）后第1天，将HGF（每天0.45mg/kg）经尾静脉注射7天（n = 12）。在对照小鼠（n = 12）中，注射0.9%氯化钠代替HGF。在MI发作4周后，在接受载体处理的对照心脏和接受HGF处理的心脏中获取血流动力学数据。在HGF处理组中，左心室压力-容积关系表明心脏功能得到良好保留。这些小鼠表现出更好的左心室收缩和舒张功能。与载体处理组相比，HGF处理心脏的梗死左心室壁更厚。HGF处理心脏的心室壁纤维化和梗死面积显著减小。在HGF处理的梗死心脏边缘区域观察到5-溴-2'-脱氧尿苷（BrdU）和Ki67阳性心肌细胞。在边缘区域和心外膜观察到c-Met和c-kit阳性心肌细胞。通过单位面积血管密度测定，HGF处理心脏的血管生成显著增强。与对照心脏相比，观察到HGF处理心脏的凋亡显著减少，且与Akt激活增加密切相关。HGF治疗通过血管生成、心室壁增厚和心肌细胞肥大改善心脏功能。HGF的抗凋亡作用由PI3激酶/Akt途径的激活介导。
