血管生成素-1对猪慢性缺血心肌中功能性新生血管增生的促进作用

Objective To investigate the long-term angiogenic effects of angiopoietin-1 (ANG-1) and vascular endothelial growth factor (VEGF) in a swine model with chronic myocardial ischemia.Method Four-weeks after gradual occlusion of the left circumflex coronary artery by Ameroid constrictor,animals were injected with recombinant adenoviral vectors carrying either human ANG-1 (AdANG-1 group,n=9),human VEGF 165 (AdVEGF group,n=10) or empty vector (n=7) into the left ventricle free wall supplied by the constricted artery.Four and twelve weeks after the gene transfer mediated by the adenovirus,regional blood flow in ischemic myocardium were respectively measured with fluorescent microsphere while immunohistochemical study were also conducted accordingly.Results Left ventricular perfusion in animals in the AdANG-1 group ［(3.25±0.16) mL min-1 g-1］ were significantly higher than that in the AdVEGF group ［(1.09±0.13) mL min-1 g-1］ and empty vector group ［(1.20±0.03) mL min-1 g-1］ 4 weeks after gene tranfer (P<0.05).Microvascular densities in the left ventricles of animals in the AdANG-1 group ［(19.61±1.76)/0.572 mm2 myocardial tissue］ and the AdVEGF group ［(18.17±1.43)/0.572 mm2 myocardial tissue］ were significantly higher than animals that received empty vector ［(13.53±0.92)/0.572 mm2 myocardial tissue］ 12 weeks after gene transfer (P<0.05).ANG-1,but not VEGF,contributed to enhanced regional perfusion by increasing arteriolar density ［(1.9±0.4)/0.572 mm2 myocardial tissue vs.(0.7±0.2)/0.572 mm2 myocardial tissue,P<0.05］ of large-sized (50-100 μm) arterioles.Conclusions Gene transfer of ANG-1 and VEGF can enhance angiogenesis,but only ANG-1 promotes sustained improvement of ventricular perfusion that expedites recovery of ischemic myocardium via arteriogenesis,which provides histoanatomical prerequisite to expedite recovery of ischemic myocardium.