TY - JOUR
T1 - Vascular endothelial growth factor modulates pulmonary vein arrhythmogenesis via vascular endothelial growth factor receptor 1/NOS pathway
AU - Chang, Jun Hei
AU - Cheng, Chen Chuan
AU - Lu, Yen Yu
AU - Chung, Cheng Chih
AU - Yeh, Yung Hsin
AU - Chen, Yao Chang
AU - Higa, Satoshi
AU - Chen, Shih Ann
AU - Chen, Yi Jen
N1 - Funding Information:
This work was supported by grants from the Ministry of Science and Technology ( MOST107-2314-B-038-101-MY3 , MOST108-2314-B-016-048 , MOST108-2314-B-281-007-MY3 , MOST109-2314-B-038-124-MY3 , MOST109-2314-B-016-045 , and MOST109-2314-B-016-001-MY2 ), Taipei Medical University-Wan Fang Hospital ( 106-swf-10 , 107-wf-swf-02 , 107-wf-swf-07 , 107-wf-eva-13 , 108-wf-eva-06 , 108-wf-swf-01 , 108-wf-swf-06 , 109-wf-eva-04 , 109-wf-eva-18 , and 109-wf-swf-09 ), the Ministry of National Defense-Medical Affairs Bureau ( MND-MAB-110-085 ), Chi-Mei Medical Center ( 105CM-TMU-13 , 106CM-TMU-08 and 108CM-TMU-05 ), and the Foundation for the Development of Internal Medicine in Okinawa, Japan ( 2-02-005 ).
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/11/15
Y1 - 2021/11/15
N2 - Atrial fibrillation (AF) is a common form of arrhythmia with serious public health impacts, but its underlying mechanisms are not yet fully understood. Vascular endothelial growth factor (VEGF) is highly expressed in the atrium of patients with AF, but whether VEGF affects AF pathogenesis remains unclear. Pulmonary veins (PVs) are important sources for the genesis of atrial tachycardia or AF. Therefore, this study assessed the effects of VEGF on PV electrophysiological properties and evaluated its underlying mechanisms. Conventional microelectrodes and whole-cell patch clamps were performed using isolated rabbit PV preparations or single isolated PV cardiomyocytes before and after VEGF or VEGF receptor (VEGFR), Akt, NOS inhibitor administration. We found that VEGF (0.1, 1, and 10 ng/mL) reduced the PV beating rate in a dose-dependent manner. Furthermore, VEGF (10 ng/mL) reduced late diastolic depolarization and diastolic tension. Isoproterenol increased PV beating and burst firing, which was attenuated by VEGF (1 ng/mL). In the presence of VEGFR-1 inhibition (ZM306416 at 10 μM) and L-NAME (100 μM), VEGF (1 ng/mL) did not alter PV spontaneous activity. In isolated PV cardiomyocytes, VEGF (1 ng/mL) decreased L-type calcium, sodium/calcium exchanger, and late sodium currents. In conclusion, we found that VEGF reduces PV arrhythmogenesis by modulating sodium/calcium homeostasis through VEGFR-1/NOS signaling pathway.
AB - Atrial fibrillation (AF) is a common form of arrhythmia with serious public health impacts, but its underlying mechanisms are not yet fully understood. Vascular endothelial growth factor (VEGF) is highly expressed in the atrium of patients with AF, but whether VEGF affects AF pathogenesis remains unclear. Pulmonary veins (PVs) are important sources for the genesis of atrial tachycardia or AF. Therefore, this study assessed the effects of VEGF on PV electrophysiological properties and evaluated its underlying mechanisms. Conventional microelectrodes and whole-cell patch clamps were performed using isolated rabbit PV preparations or single isolated PV cardiomyocytes before and after VEGF or VEGF receptor (VEGFR), Akt, NOS inhibitor administration. We found that VEGF (0.1, 1, and 10 ng/mL) reduced the PV beating rate in a dose-dependent manner. Furthermore, VEGF (10 ng/mL) reduced late diastolic depolarization and diastolic tension. Isoproterenol increased PV beating and burst firing, which was attenuated by VEGF (1 ng/mL). In the presence of VEGFR-1 inhibition (ZM306416 at 10 μM) and L-NAME (100 μM), VEGF (1 ng/mL) did not alter PV spontaneous activity. In isolated PV cardiomyocytes, VEGF (1 ng/mL) decreased L-type calcium, sodium/calcium exchanger, and late sodium currents. In conclusion, we found that VEGF reduces PV arrhythmogenesis by modulating sodium/calcium homeostasis through VEGFR-1/NOS signaling pathway.
KW - Atrial fibrillation
KW - Electrophysiology
KW - Pulmonary veins
KW - Vascular endothelial growth factor
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U2 - 10.1016/j.ejphar.2021.174547
DO - 10.1016/j.ejphar.2021.174547
M3 - Article
C2 - 34624234
AN - SCOPUS:85116574574
SN - 0014-2999
VL - 911
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 174547
ER -