- 作者: Winston S.N. Shim; Wei Li; Li Zhang; Shiqi Li; Hwee Choo Ong; In-Chin Song; Akanksha Bapna; Ruowen Ge; Yean Teng Lim; Seng Chye Chuah; Eugene K.W. Sim; Philip Wong
- 作者服務機構: 1 Research and Development Unit, National Heart Center, 17 Third Hospital Avenue, Singapore, 168752, Singapore; ; 2 Department of Surgery, National University of Singapore, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore; ; 3 Department of Experimental Surgery, Singapore General Hospital, 17 Third Hospital Avenue, Singapore, 168752, Singapore; ; 4 Department of Biological Sciences, National University of Singapore, 10 Kent Ridge Crescent, Singapore, 119074, Singapore; ; 5 Cardiac Department, National University Hospital, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore; ; 6 Department of Cardiology, National Heart Center, 17 Third Hospital Avenue, Singapore, 168752, Singapore
- 中文摘要: --
- 英文摘要: This study investigates the long-term angiogenic effects of ANG-1 and VEGF in a swine chronic myocardial ischemia model. 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 (n = 9), human VEGF 165 (n = 10) or empty vector (n = 7) into the left ventricle free wall supplied by the constricted artery. Left ventricular perfusion in animals that received AdANG-1 (3.25 ± 0.16 ml/min/g, p<0.05) recovered robustly 4 weeks after gene transfer while ischemia persisted in the AdVEGF (1.09 ± 0.13 ml/min/ g) and empty vector (1.20 ±0.03 ml/min/g) groups. Microvascular densities in the left ventricles of animals that received AdANG-1 (19.61 ± 1.76/0.572 mm2 myocardial tissue, p<0.05) and AdVEGF (18.17 ± 1.43/ 0.572 mm2 myocardial tissue, p < 0.05) were significantly higher than animals that received empty vector (13.53 ±0.92/0.572 mm2 myocardial tissue) 12 weeks after gene transfer. 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. These data demonstrate that gene transfer of ANG-1 and VEGF enhances angiogenesis, but ANG-1 promotes sustained improvement of ventricular perfusion that expedites recovery of ischemic myocardium via arteriogenesis.
- 中文關鍵字: --
- 英文關鍵字: angiogenesis, angiopoietin, ischemia, regional perfuison