Abstract
TRPM2 is a cation channel involved in calcium influx in response to cellular oxidative stress. We hypothesized that TRPM2 regulates VEGF induced vascular angiogenesis secondary to ROS production. We show that TRPM2 knockdown suppressed VEGF induced human lung endothelial cell (hLEC) hyper‐permeability, which is essential for angiogenesis, as measured by trans‐endothelial resistance and albumin influx (EBA). VEGF induced phosphorylation of VE cadherin at Tyr658 residue was inhibited by TRPM2 knockdown. Additionally, VEGF stimulation increased ROS production in hLEC, and application of apocynin (ROS scavenger) inhibited VEGF induced phosphorylation of Tyr658 of VE cadherin. TRPM2 knockdown reduced VEGF induced calcium entry in hLEC, and delayed migration of HUVEC. VEGF induced angiogenesis measured by in vivo matrigel plug assay was markedly reduced in TRPM2 KO mice compared to wild type. We conclude that calcium influx from ROS activated TRPM2 channels on VEGF stimulation is a key mechanism signaling angiogenesis.Research support: NIH grants RO1 HL45638‐23 and P01 HL077806
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