Transient Repetitive Exposure to Low Level Light Therapy Enhances Collateral Blood Vessel Growth in The Ischemic Hindlimb of The Tight Skin Mouse

The tight skin mouse (Tsk−/+) is a model of scleroderma characterized by impaired vasoreactivity, increased oxidative stress, attenuated angiogenic response to VEGF and production of the angiogenesis inhibitor angiostatin. Low‐level light therapy (LLLT) stimulates angiogenesis in myocardial infarction and chemotherapy‐induced mucositis. We hypothesize that repetitive LLLT restores vessel growth in the ischemic hindlimb of Tsk−/+ mice by attenuating angiostatin and enhancing angiomotin effects in vivo. C57Bl/6J and Tsk−/+ mice underwent ligation of the femoral artery. Relative blood flow to the foot was measured using a laser Doppler imager. Tsk−/+ mice received LLLT (670 nm, 50 mW cm−2, 30 J cm−2) for 10 min per day for 14 days. Vascular density was determined using lycopersicom lectin staining. Immunofluorescent labeling, Western blot analysis and immunoprecipitation were used to determine angiostatin and angiomotin expression. Recovery of blood flow to the ischemic limb was reduced in Tsk−/+ compared with C57Bl/6 mice 2 weeks after surgery. LLLT treatment of Tsk−/+ mice restored blood flow to levels observed in C57Bl/6 mice. Vascular density was decreased, angiostatin expression was enhanced and angiomotin depressed in the ischemic hindlimb of Tsk−/+ mice. LLLT treatment reversed these abnormalities. LLLT stimulates angiogenesis by increasing angiomotin and decreasing angiostatin expression in the ischemic hindlimb of Tsk−/+ mice.