title: Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2.
abstract: It is known that low level laser therapy is able to improve skin flap viability by increasing angiogenesis. However, the mechanism for new blood vessel formation is not completely understood. Here, we investigated the effects of 660 nm and 780 nm lasers at fluences of 30 and 40 J/cm(2) on three important mediators activated during angiogenesis. Sixty male Wistar rats were used and randomly divided into five groups with twelve animals each. Groups were distributed as follows: skin flap surgery non-irradiated group as a control; skin flap surgery irradiated with 660 nm laser at a fluence of 30 or 40 J/cm(2) and skin flap surgery irradiated with 780 nm laser at a fluence of 30 or 40 J/cm(2). The random skin flap was performed measuring 10×4 cm, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was performed on 24 points covering the flap and surrounding skin immediately after the surgery and for 7 consecutive days thereafter. Tissues were collected, and the number of vessels, angiogenesis markers (vascular endothelial growth factor, VEGF and hypoxia inducible factor, HIF-1α) and a tissue remodeling marker (matrix metalloproteinase, MMP-2) were analyzed. LLLT increased an angiogenesis, HIF-1α and VEGF expression and decrease MMP-2 activity. These phenomena were dependent on the fluences, and wavelengths used. In this study we showed that LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1α expression in a dose dependent manner.
authors.affiliation: Department of Physiotherapy, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cury
authors.forename: Ana Iochabel Soares
authors.initials: AI
authors.lastname: Moretti
authors.forename: Lívia
authors.initials: L
authors.lastname: Assis
authors.forename: Paulo
authors.initials: P
authors.lastname: Bossini
authors.forename: Jaqueline de Souza
authors.initials: Jde S
authors.lastname: Crusca
authors.forename: Carlos Benatti
authors.initials: CB
authors.lastname: Neto
authors.forename: Renan
authors.initials: R
authors.lastname: Fangel
authors.forename: Heraldo Possolo
authors.initials: HP
authors.lastname: de Souza
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: Nivaldo Antonio
authors.initials: NA
authors.lastname: Parizotto
mesh_terms: D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000532:radiotherapy*; D028022:Low-Level Light Therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000528:radiation effects; D013524:Surgical Flaps / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat
keywords: Angiogenesis; HIF1-α; Hypoxia; LLLT; MMP-2; VEGF