Far Infrared Therapy Inhibits Vascular Endothelial Inflammation via the Induction of Heme Oxygenase-1

Abstract

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,...

Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival

“…Human umbilical vein endothelial cells (HUVEC) or human aortic endothelial cells (HAEC) were purchased from Lonza (Allendale, NJ) and serially cultured on gelatin-coated dishes, as we previously described (28). Cells were propagated in M199 medium supplemented with 20% bovine calf serum, 2 mM L-glutamine, 50 g/ml endothelial cell growth factor, 90 g/ml heparin, and 100 U/ml of penicillin and streptomycin in an atmosphere of 95% air-5% CO 2.…”

“…Membranes were prehybridized for 4 h at 68°C in rapid hybridization buffer (Amersham, Arlington Heights, IL) and then incubated overnight at 68°C in hybridization buffer containing [ 32 P]DNA probes (1 ϫ 10 8 cpm) for HO-1, Nrf2, or 18S mRNA. DNA probes were generated by RT-PCR and labeled with [ 32 P]dCTP using a random priming kit (Amersham, Arlington Heights, IL) (28). After hybridization, membranes were washed and exposed to X-ray film at Ϫ70°C, and HO-1 expression was quantified by scanning densitometry and normalized with respect to 18S rRNA.…”

Novel Paradigms for Dialysis Vascular Access

“…The nonthermal effects induce eNOS expression, inhibit neointimal hyperplasia, and reduce oxidative stress. In a clinical study in dialysis access, FIR increased access blood flow and unassisted patency through AVFs (59), likely through activation of HO-1 pathways and reduction in endothelial inflammation (60). A recent randomized controlled trial showed that FIR improves the access blood flow, maturation, and long-term patency of newly created AVFs in patients with CKD stages 4 and 5 (61).…”

Novel Therapies for Hemodialysis Vascular Access Dysfunction

“…This treatment involves the application of electromagnetic radiation (wavelengths of 3-25 mm) to the skin surface overlying the vascular access. The electromagnetic radiation, which travels 2-3 cm below the skin surface, is hypothesized to be beneficial for the vasculature by inducing vasodilation, decreasing oxidative stress (82), inhibiting cell proliferation (83), and inducing protective enzymes, such as heme oxygenase-1 (84). The emitting device is positioned approximately 25 cm above the arm for 30-60 minutes per treatment.…”