Far-Infrared Mitigates Vascular Endothelial Growth Factor-Induced Proliferation in Human Umbilical Vein Endothelial Cells Via the Generation of Nitric Oxide and Reactive Oxygen Species

(Poster of Annual meeting of ASN 2008)
Yung-Ho Hsu, Tso-Hsiao Chen, Chun-Cheng Hou, Yuh-Mou Sue, Cheng-Hsien Chen Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan

Vascular access dysfunction causes enormous clinical morbidity in hemodialysis patients. Venous stenosis as a result of neointimal hyperplasia is the major cause of it. Far-infrared (FIR) therapy has been reported recently as a competent therapeutic modality in improving access flow and patency of the arteriovenous fistula. But the exact mechanism remains to be determined. The present study aims to evaluate the influence of FIR on vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVEC) and examine the mechanisms. VEGF-induced proliferation of HUVEC was significantly reduced by FIR at 20 mili watt (mw)/cm2 for 30min in comparison with those without FIR radiation. The VEGF-induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in HUVEC was also inhibited by FIR. These effects were not obvious by the thermal effect in HUVEC alone from 37.5 to 38oC, as the FIR treatment increased the cultured medium temperature approximately 0.5oC. We found FIR treatment induced the phosphorylation of endothelial nitric oxide synthase (eNOS) and increased nitric oxide (NO) in HUVEC. The NOS inhibitor N G -nitro-l-arginine methylester (L-NAME) abolished the inhibitory effects of FIR on cell proliferation and the phosphorylation of ERK1/2. FIR also induced reactive oxygen species (ROS) generation in HUVEC. The NADH oxidase inhibitors and ROS scavengers blocked the inhibitory effect of FIR on cell proliferation, and significantly reduced FIR-induced eNOS phosphorylation. We also found that Src homology 2- containing tyrosine phosphatase (SHP-2) was associated with phospho-eNOS and transiently oxidized to inhibit the dephosphorylation of phosphor-eNOS during FIR treatment. These data suggest that FIR, through its nonthermal effects, induces NO and ROS generation to mitigate VEGF-induced proliferation in HUVEC.