Neuropilin-1 is essential for enhanced VEGF(165)-mediated vasodilatation in collateral-dependent coronary arterioles of exercise-trained pigs.
Neuropilin-1 is essential for enhanced VEGF(165)-mediated vasodilatation in collateral-dependent coronary arterioles of exercise-trained pigs.
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DOI：
10.1159/000152351
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发表时间：
2009
影响因子：
1.7
通讯作者：
中科院分区：
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--
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运动训练可增强侧枝依赖性冠状动脉中血管内皮生长因子（VEGF165）的血管舒张作用。据报道，VEGF 受体 2 (VEGFR-2) 与非酪氨酸激酶受体、neuropilin-1 的相互作用可增强 VEGF165 介导的信号传导。在当前的研究中，我们测试了以下假设：neuropilin-1 介导运动增强的 VEGF165 介导的侧支依赖性小动脉血管舒张，以及这些小动脉中的 Neuropilin-1 和/或 VEGFR-2 蛋白水平增加。通过手术将 Ameroid 封堵器放置在小型猪的近端左回旋冠状动脉周围。手术后八周，动物被随机分为静坐或运动训练（跑步机跑步；每周 5 天；14 周）方案。从侧支依赖性和对照（左前降支）心肌区域分离冠状动脉（直径约 100 μm），并通过体外视频显微镜进行研究或冷冻进行免疫印迹分析。通过抑制 VEGF165-neuropilin-1 相互作用，可以逆转运动增强的 VEGF165 介导的侧支依赖性小动脉血管舒张作用。 VEGF121 不与 Neuropilin-1 相互作用，在所有治疗组的小动脉中诱导类似的血管舒张。免疫印迹显示，经过运动训练的猪的侧支依赖性小动脉中的 VEGFR-1、VEGFR-2 和 Neuropilin-1 蛋白水平显着升高。 Neuropilin-1 在运动增强的 VEGF165 介导的侧支依赖性冠状动脉血管舒张中发挥着至关重要的作用，并且与 Neuropilin-1 受体蛋白水平增加相关。
Exercise training enhances vasodilatation to vascular endothelial growth factor (VEGF165) in collateral-dependent coronary arterioles. Interaction of VEGF receptor 2 (VEGFR-2) and the non-tyrosine-kinase receptor, neuropilin-1 has been reported to potentiate VEGF165-mediated signaling. In the current study, we tested the hypotheses that neuropilin-1 mediates the exercise-enhanced VEGF165-mediated vasodilatation in collateral-dependent arterioles and that neuropilin-1 and/or VEGFR-2 protein levels are increased in these arterioles. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Eight weeks after surgery, the animals were randomized into sedentary or exercise training (treadmill run; 5 days/week; 14 weeks) protocols. Coronary arterioles (~100 μm diameter) were isolated from both collateral-dependent and control (left anterior descending) myocardial regions and studied by in vitro videomicroscopy or frozen for immunoblot analysis. Exercise-enhanced VEGF165-mediated vasodilatation in collateral-dependent arterioles was reversed by inhibition of the VEGF165-neuropilin-1 interaction. VEGF121, which does not interact with neuropilin-1, induced similar vasodilatation in arterioles from all treatment groups. Immunoblot revealed significantly elevated VEGFR-1, VEGFR-2 and neuropilin-1 protein levels in collateral-dependent arterioles of exercise-trained pigs. Neuropilin-1 plays a vital role in the exercise-enhanced VEGF165-mediated vasodilatation of collateral-dependent coronary arterioles and is associated with increased neuropilin-1 receptor protein levels.
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