Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve
Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve
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DOI：
10.1161/hc3201.095192
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发表时间：
2001-08-14
期刊：
影响因子：
37.8
通讯作者：
Nabel, EG
中科院分区：
文献类型：
--
作者：
Rajagopalan, S;Shah, M;Nabel, EG
背景-血管内皮生长因子（VEGF）目前正在外周动脉疾病患者的临床血管生成试验中进行评估。我们假设使用腺病毒载体（Ad（GV）VEGF（121.10））将VEGF递送至下肢骨骼肌将改善外周内皮功能。因此，我们调查了参加I期腺病毒介导的VEGF基因递送试验的患者的下肢内皮功能（121.10），方法和结果-在基线和Ad（GV）VEGF给药后30天，通过热稀释法测量指标肢体的血流量（121.10），响应于向同侧股动脉输注内皮依赖性和非依赖性激动剂（分别为乙酰胆碱和硝酸甘油）。Ad（GV）VEGF治疗前后的基础流量无差异（121.10）。对于乙酰胆碱（150 μ g/min和300 μ g/min），Ad（GV）/TGF（121.10）治疗前的流量变化为0.9倍（0.33 +/-0.03至0.32 +/-0.03 L/min）和1.2倍（0.33 +/- 0.03至0.490 +/- 0.02 L/min）。Ad（GV）VEGF（121.10）治疗后，血流量分别增加2.4倍（0.310 ± 0.04至0.730 ± 0.10 L/min）和2.3倍（0.31 ± 0.04至0.7 ± 0.08 L/min）（P
Background-Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (Ad(GV)VEGF(121.10)) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF(121.10),Methods and Results-Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of Ad(GV)VEGF(121.10), in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with Ad(GV)VEGF(121.10). In response to acetylcholine (150 mug/min and 300 mug/min), there was a 0.9-fold (0.33 +/- 0.03 to 0.32 +/- 0.03 L/min) and 1.2-fold (0.33 +/- 0.03 to 0.490 +/- 0.02 L/inin) change in flow before Ad(GV)/TGF(121.10) treatment. After Ad(GV)VEGF(121.10) treatment, flow increased 2.4-fold (0.310 +/- 0.04 to 0.730 +/- 0.10 L/min) and 2.3-fold (0.31 +/- 0.04 to 0.7 +/- 0.08 L/min), respectively (P