THERAPEUTIC ANGIOGENESIS - A SINGLE INTRAARTERIAL BOLUS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AUGMENTS REVASCULARIZATION IN A RABBIT ISCHEMIC HIND-LIMB MODEL
THERAPEUTIC ANGIOGENESIS - A SINGLE INTRAARTERIAL BOLUS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AUGMENTS REVASCULARIZATION IN A RABBIT ISCHEMIC HIND-LIMB MODEL
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DOI：
10.1172/jci117018
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发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
ISNER, JM
中科院分区：
文献类型：
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作者：
TAKESHITA, S;ZHENG, LP;ISNER, JM
血管内皮生长因子（VEGF）是一种肝素结合的内皮细胞特异性丝裂原。以前的研究表明，VEGF是自然发生的生理和病理性血管生成的调节剂。在这项研究中，我们调查的假设，血管生成的潜力，VEGF是足以构成一个治疗效果。将VEGF的可溶性165-氨基酸同种型作为单次动脉内推注给予兔的髂内动脉，其中切除同侧股动脉以诱导严重的单侧后肢缺血。500- 1，000 μ g剂量的VEGF通过血管造影术以及通过组织学的毛细血管数目产生统计学显著的侧支血管发育增加;接受VEGF治疗的动物对缺血肢体血流动力学缺陷的改善明显大于未治疗的对照组（小腿血压比，0.7 +/- 0.14 vs. 0.48 +/- 0.19，P < 0.05）。连续血管造影显示，在9只VEGF治疗动物中，7只动物的起源侧支动脉（干动脉）逐渐线性延伸至载瘤血管（折返动脉）重建的远端点。这些发现为VEGF的血管生成活性足以实现治疗益处的概念建立了原则证据。这种策略最终可能适用于继发于动脉闭塞性疾病的严重肢体缺血患者。
Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intraarterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 mu g of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.7 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.