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.
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http://dx.doi.org/10.1016/j.ejphar.2021.174547 | DOI Listing |
Drug Des Devel Ther
December 2024
Department of Cardiology, Guang Anmen Hospital, Beijing, People's Republic of China.
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View Article and Find Full Text PDFBiotechnol J
December 2024
Department of Biomedical Engineering, Tulane University, New Orleans, USA.
Microphysiological systems (MPS) containing perfusable vascular beds unlock the ability to model tissue-scale elements of vascular physiology and disease in vitro. Access to inexpensive stereolithography (SLA) 3D printers now enables benchtop fabrication of polydimethylsiloxane (PDMS) organ chips, eliminating the need for cleanroom access and microfabrication expertise, and can facilitate broader adoption of MPS approaches in preclinical research. Rapid prototyping of organ chip mold designs accelerates the processes of design, testing, and iteration, but geometric distortion and surface roughness of SLA resin prints can impede the development of standardizable manufacturing workflows.
View Article and Find Full Text PDFClin Appl Thromb Hemost
December 2024
Department of Cardiology, Health Sciences Division, Loyola University Chicago, Maywood, IL, USA.
Angiopoeitin-2 (Ang2) is a vascular growth factor involved in regulating angiogenesis and endothelial remodeling. Higher Ang2 levels have been associated with mortality in the general population and among male hemodialysis patients, but its effects on concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) are unknown. Plasma samples from 73 ESRD patients and 40 healthy patients were analyzed for Ang2 concentrations using ELISA.
View Article and Find Full Text PDFInt Ophthalmol Clin
January 2025
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Retinopathy of prematurity (ROP) remains a significant health care concern in neonatal care as advances in neonatal intensive practices have improved the survival rates of premature infants. The management and screening of ROP have evolved significantly, with notable trends and advancements aimed at improving outcomes. The use of intravitreal antivascular endothelial growth factor injections has emerged as a prominent initial treatment for ROP in addition to laser photocoagulation.
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