Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
Biomed Pharmacother. 2017 Jan;85:697-703. doi: 10.1016/j.biopha.2016.11.082. Epub 2016 Dec 7.
The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (I) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). I and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased I in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced I increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, I can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases.
血管内皮生长因子 165（VEGF165）对心肌细胞电生理特性的作用机制尚未完全阐明。本研究旨在验证以下假说，即作为血管生成启动因子的 VEGF165 通过作用于血管内皮生长因子受体 2（VEGFR2）影响心肌细胞的 L 型钙电流（I）和细胞膜电位。通过全细胞膜片钳技术，在不同浓度 VEGF165 蛋白处理的分离豚鼠心室肌细胞中记录 I 和动作电位（AP）。使用 VEGFR2 抑制剂，我们还测试了 VEGF165 在心肌细胞中的受体。结果发现，VEGF165 呈浓度依赖性增加 I。VEGFR2 抑制剂 SU5416 几乎完全消除了 VEGF165 诱导的 I 增加。VEGF165 对动作电位 90（APD90）和 AP 的其他特性没有显著影响。我们的结论是，在豚鼠心室肌细胞中，VEGF165 通过与 VEGFR2 结合以浓度依赖的方式增加 I，而不会导致动作电位时程发生任何显著改变。本研究结果可能进一步阐明了 VEGF165 在心脏病干预中的安全性。
