Background and Objectives: The purpose of this study, therefore, was to determine the mechanisms by which lowenergy laser irradiation (LELI) may exert some of its angiogenic effects via the PI3 kinase/eNOS signaling pathway and induce endothelial cell migration and neovascularization, an important and necessary part of wound healing. Study Design/Materials and Methods: The possible molecular mechanism of helium-neon (He-Ne) laser irradiation on endothelial cells was proposed. He-Ne laser at 632.5 nm was used to stimulate human umbilical vein endothelial cell (HUVEC), and its effect on cell proliferation, nitric oxide secretion, and cell migration was determined. Results: Irradiation enhanced endothelial nitric oxidase synthase (eNOS) protein expression, and irradiation of less than 0.26 J/cm 2 enhanced eNOS gene expression in HUVEC. The cell migration ability was promoted for HUVEC irradiated with 0.26 J/cm 2 . This agreed with the vinculin protein expression induced by irradiation. In addition, the angiogenesis was promoted. The induced eNOS expression was inhibited by LY294002, indicating that the effect of laser on EC could be attributed to the upregulation of eNOS expression through PI3K pathway at the cellular and molecular levels as a result of the He-Ne laser. Conclusions: The study has shown that LELI increased endothelial cell proliferation, migration, NO secretion, and identified that activation of PI3K/Akt pathway was a critical step for the elevated for eNOS expression upon LELI.
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