title: Far red/near infrared light treatment promotes femoral artery collateralization in the ischemic hindlimb.
abstract: Nitric oxide (NO) is a crucial mediator of hindlimb collateralization and angiogenesis. Within tissues there are nitrosyl-heme proteins which have the potential to generate NO under conditions of hypoxia or low pH. Low level irradiation of blood and muscle with light in the far red/near infrared spectrum (670 nm, R/NIR) facilitates NO release. Therefore, we assessed the impact of red light exposure on the stimulation of femoral artery collateralization. Rabbits and mice underwent unilateral resection of the femoral artery and chronic R/NIR treatment. The direct NO scavenger carboxy-PTIO and the nitric oxide synthase (NOS) inhibitor L-NAME were also administered in the presence of R/NIR. DAF fluorescence assessed R/NIR changes in NO levels within endothelial cells. In vitro measures of R/NIR induced angiogenesis were assessed by endothelial cell proliferation and migration. R/NIR significantly increased collateral vessel number which could not be attenuated with L-NAME. R/NIR induced collateralization was abolished with c-PTIO. In vitro, NO production increased in endothelial cells with R/NIR exposure, and this finding was independent of NOS inhibition. Similarly R/NIR induced proliferation and tube formation in a NO dependent manner. Finally, nitrite supplementation accelerated R/NIR collateralization in wild type C57Bl/6 mice. In an eNOS deficient transgenic mouse model, R/NIR restores collateral development. In conclusion, R/NIR increases NO levels independent of NOS activity, and leads to the observed enhancement of hindlimb collateralization.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, USA. ntonn@mcw.edu
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Lohr
authors.forename: James T
authors.initials: JT
authors.lastname: Ninomiya
authors.forename: David C
authors.initials: DC
authors.lastname: Warltier
authors.forename: Dorothée
authors.initials: D
authors.lastname: Weihrauch
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D005263:Femoral Artery / Q000473:pathology* / Q000528:radiation effects*; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000528:radiation effects; D006801:Humans; D007511:Ischemia / Q000473:pathology; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits
chemical_list: D009569:Nitric Oxide
keywords: Angiogenesis; HUVEC; Hindlimb collateralization; Low level light therapy; NO; NOS; Nitric oxide; Nitrosyl-hemoglobin; R/NIR; VEGF; human umbilical vein endothelial cell; nitric oxide; nitric oxide synthase; red/near infrared light wavelength peak at 670nm; vascular endothelial growth factor