title: Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.
abstract: 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 (ICa,L) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). ICa,Land 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 ICa,Lin a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced ICa,Lincrease. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, ICa,Lcan 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.
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
authors.forename: Wenlu
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China. Electronic address: gaocy6208@163.com.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China; Main Line Health Heart Center, Lankenau Institute for Medical Research, Wynnewood, PA, USA.
authors.forename: Datun
authors.initials: D
authors.lastname: Qi
authors.affiliation: Henan Institute of Cardiovascular Epidemiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Hao
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China.
authors.forename: Guoyou
authors.initials: G
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, Henan 450003, China; Main Line Health Heart Center, Lankenau Institute for Medical Research, Wynnewood, PA, USA.
authors.forename: Ganxin
authors.initials: G
authors.lastname: Yan
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009543:Nifedipine
keywords: Action potential; Cardiac myocytes; L-type calcium current; VEGF165; VEGFR2