Objective-Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation. Methods and Results-Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-␣-mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis. Key Words: endothelium Ⅲ far infrared therapy Ⅲ inflammation Ⅲ leukocyte adhesion A well-functioning vascular access is necessary for achieving adequate hemodialysis (HD) in patients with end stage renal failure. Approximately 17% to 25% of HD patient hospitalizations in the United States arise from vascular access complications, with an annual cost of more than 1 billion US dollars, which continues to grow. 1 Nearly 85% of vascular access failures arise from thromboses, more than 80% of which are associated with stenoses, 2 which usually presents with inadequate blood flow. 3,4 The causative factors of vascular access stenosis include small diameter of artery and vein, surgical technique, previous venipunctures, hemodynamic stress, and the presence of accessory veins. 5 Moreover, many factors leading to endothelial dysfunction, such as oxidative stress, hyperhomocysteinemia, platelet activation, and inflammation are associated with arteriovenous fistula (AVF) failure. 5 The histological features of vascular access stenosis comprise vascular inflammation, intimal hyperplasia, and excessive accumulation of extracellular matrix. 5 Despite these findings, the cause of stenoses remains unknown in a significant proportion of HD patients. This interindividual variation may relate to differences in the genetic background that may influence susceptibility to vascular inflammation and neointima formation after endothelial and smooth muscle injury. 6,7 Consistent with this notion, AVF survival was reported to be associated with specific genetic polymorphisms of transforming growth factor (TGF)-1 8 and methylene tetrahydrofolate reductase. 9 In addition, we recently identified a length polymorphism in the heme oxygenase-1 (HO-1) gene that is associated with patency of AVFs. 10 HO-1 catalyzes the oxidative degradation of heme into equimolar amounts of biliverdin,...
