Lazarous D F, Shou M, Scheinowitz M, Hodge E, Thirumurti V, Kitsiou A N, Stiber J A, Lobo A D, Hunsberger S, Guetta E, Epstein S E, Unger E F
Experimental Physiology and Pharmacology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1650, USA.
Circulation. 1996 Sep 1;94(5):1074-82. doi: 10.1161/01.cir.94.5.1074.
We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo.
Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury.
Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.
我们已经表明，血管生成肽碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）在给药≥4周时可促进犬冠状动脉侧支循环的发育。bFGF是一种中胚层来源细胞的多能有丝分裂原，理论上可能会加剧内膜平滑肌细胞增生，而这是动脉粥样硬化的一个基本组成部分。VEGF是一种内皮细胞特异性有丝分裂原和血管通透性因子，可能会产生与血管高通透性相关的有害影响。本研究有两个目的：（1）确定用bFGF或VEGF进行短期（7天）全身动脉治疗是否能改善心肌侧支灌注，以及（2）确定这些肽是否会在体内诱导内膜积聚。
犬接受阿霉素诱导的左旋冠状动脉闭塞，并随机分为每日经左心房推注bFGF 1.74 mg（n = ⑨）、VEGF 0.72 mg（n = ⑨）或生理盐水（n = ⑩）组（第10至1⒍天）。另外的犬随机分为VEGF 0.72 mg（n = ⑥）或生理盐水（n = ⑤）组；然而，治疗延迟了1周。与开始治疗同时，所有犬均接受了股动脉球囊剥脱损伤。bFGF显著增加了最大侧支血流，但未加剧内膜积聚。VEGF对最大侧支血流没有明显影响，但它加剧了血管损伤后的内膜增厚。
bFGF短期治疗可促进侧支循环发育，而不会增加血管损伤部位的内膜积聚。尽管本研究中使用的VEGF没有增加侧支循环发育，但它显著加剧了内膜积聚。这些数据为bFGF在特定缺血性心脏病患者中的临床研究提供了支持。
