SITE-SPECIFIC THERAPEUTIC ANGIOGENESIS AFTER SYSTEMIC ADMINISTRATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR
SITE-SPECIFIC THERAPEUTIC ANGIOGENESIS AFTER SYSTEMIC ADMINISTRATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR
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DOI：
10.1016/s0741-5214(95)70272-5
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发表时间：
1995-02-01
影响因子：
4.3
通讯作者：
ISNER, JM
中科院分区：
文献类型：
--
作者：
BAUTERS, C;ASAHARA, T;ISNER, JM
目的：最近的实验研究已经确定了治疗性血管生成的可行性；在所有病例中，这都是通过局部应用血管生成生长因子来实现的。方法：新西兰大白兔一侧肢体结扎髂外动脉，切断股总动脉和股浅动脉10天后，分别给予肝素(800IU，n=13)、血管内皮生长因子(1 mg，n=3；5 mg，n=5)、肝素(800IU，n=5)+血管内皮生长因子(1 mg，n=5)；耳缘静脉注射5 mg(n=7)或生理盐水(n=8)。结果：两组动物在第10天(对照组，0.44+/-0.02；肝素，0.47+/-0.02；血管内皮生长因子，0.60+/-0.01；肝素+血管内皮生长因子，0.61+/-0.02)和第30天(对照组，0.49+/-0.05；肝素，0.48+/-0.02；血管内皮生长因子0.70+/-0.03；肝素+血管内皮生长因子0.73+/-0.03)。在第30天，两组血管造影评分均显著高于对照组(P<；0.05)(对照组，0.28+/-0.01；肝素，0.28+/-0.01；血管内皮细胞生长因子，0.37+/-0.01；肝素+/-血管内皮生长因子，0.38+/-0.02)。血管内皮生长因子治疗组缺血肢体第30天的最大血流储备高于对照组(1.87+/-0.07；肝素，1.92+/-0.08；血管内皮生长因子，2.42+/-0.16；肝素+/-血管内皮生长因子，2.33+/-0.12)。血管内皮生长因子处理组兔缺血肌肉毛细血管密度较高(P<；0.01)(对照组156+/-10/mm(2)；肝素，178+/-8/mm(2)；血管内皮生长因子，230+/-10/mm(2)；肝素+血管内皮生长因子，233+/-8/mm(2))。结论：无论有无肝素，静脉注射血管内皮生长因子均可促进兔缺血后肢侧支血管的形成。血管内皮生长因子单次推注全身给药可能是一种可行的治疗策略。
Purpose: Recent experimental studies have established the feasibility of therapeutic angiogenesis; in all cases, this has been achieved with local administration of angiogenic growth factors. This study was designed to investigate the hypothesis that systemic administration of an angiogenic growth factor specifically mitogenic for endothelial cells-vascular endothelial growth factor (VEGF)-could augment collateral vessel development in a rabbit ischemic hindlimb model.Methods: Ten days after the Ligation of the external iliac artery and excision of the common and superficial femoral arteries in one limb of New Zealand white rabbits, heparin (800 IU, n = 13), VEGF (1 mg, n = 3; 5 mg, n = 5), heparin (800 IU) + VEGF (1 mg, n = 5; 5 mg, n = 7), or saline solution (n = 8) was injected as a single bolus in a marginal ear vein. Collateral vessel formation and limb perfusion were assessed 10 and 30 days after treatment.Results: Animals in both VEGF-treated groups had a significantly higher (p < 0.01) increase in calfblood pressure ratio at day 10 (control, 0.44 +/- 0.02; heparin, 0.47 +/- 0.02; VEGF, 0.60 +/- 0.01; heparin + VEGF, 0.61 +/- 0.02) and day 30 (control, 0.49 +/- 0.05; heparin, 0.48 +/- 0.02; VEGF, 0.70 +/- 0.03; heparin + VEGF, 0.73 +/- 0.03). Both VEGF-treated groups had a significantly higher (p < 0.05) angiographic score at day 30 (control, 0.28 +/- 0.01; heparin, 0.28 +/- 0.01; VEGF, 0.37 +/- 0.01; heparin +/- VEGF, 0.38 +/- 0.02). Maximum flow reserve at day 30 in the ischemic limb was higher (p < 0.05) in VEGF-treated rabbits (control, 1.87 +/- 0.07; heparin, 1.92 +/- 0.08; VEGF, 2.42 +/- 0.16; heparin +/- VEGF, 2.33 +/- 0.12). Capillary density was higher (p < 0.01) in the ischemic muscles of VEGF-treated rabbits (control, 156 +/- 10/mm(2); heparin, 178 +/- 8/mm(2); VEGF, 230 +/- 10/mm(2); heparin + VEGF, 233 +/- 8/mm(2)).Conclusions: This series of in vivo experiments demonstrates that intravenous administration of VEGF, with or without heparin, results in both anatomic and physiologic evidence of enhanced collateral vessel formation in the rabbit ischemic hindlimb. Single-bolus systemic administration of VEGF may be a feasible therapeutic strategy in patients with lower-extremity ischemia.