Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan, China
J Am Heart Assoc. 2018 Jan 26;7(3):e007730. doi: 10.1161/JAHA.117.007730.
Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters.
I and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, =0.001; 12.73±0.34 versus 9.05±1.20, n=5, =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I), resting membrane potential, AP amplitude, or maximal velocity of depolarization.
VEGF inhibited I in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia.
血管内皮生长因子（VEGF）通过其血管生成特性对缺血性心肌发挥多种有益作用。然而，目前尚不清楚 VEGF 是否对心肌细胞的电生理特性有直接影响。本研究旨在探讨不同浓度的 VEGF 对豚鼠心室肌细胞延迟整流钾电流（I）的影响及其对动作电位（AP）参数的影响。
采用全细胞膜片钳技术记录心室肌细胞的 I 和 AP。在记录前，将细胞用对照液或含不同浓度 VEGF 的溶液灌流 10 分钟。部分心室肌细胞在加入 VEGF 前先用磷脂酰肌醇 3-激酶抑制剂预处理 1 小时。结果发现，VEGF 呈浓度依赖性抑制缓慢激活的延迟整流钾电流（I）（18.13±1.04 对 12.73±0.34，n=5，=0.001；12.73±0.34 对 9.05±1.20，n=5，=0.036），延长 AP 时程（894.5±36.92 对 746.3±33.71，n=5，=0.021）。PI3K 抑制剂wortmannin 消除了这些 VEGF 诱导的作用。VEGF 对快速激活的延迟整流钾电流（I）、静息膜电位、AP 幅度或去极化最大速度无显著影响。
VEGF 通过 PI3K 介导的信号通路呈浓度依赖性抑制 I，导致 AP 延长。这些结果表明 VEGF 具有预防高交感神经活性和缺血条件下室性心律失常的潜在治疗作用。
