Daisuke Kurumazukaa, Hisashi Shirakawaa, Sayaka Kimuraa, Tatsuhiko Morib, Yasuo Matsumuraa and Masanori Takaokac
Background: It has been reported that α-lipoic acid is an anti-oxidative and anti-inflammatory agent, and exhibits beneficial effects in experimental disease models such as hypertension and acute kidney injury. In the present study, we examined effects of α-lipoic acid on neointimal hyperplasia in balloon-injured carotid arteries. Methods: Male rats underwent balloon injury of the right carotid artery with a 2F Fogarty balloon catheter. α- Lipoic acid was administrated to balloon-injured rats in the following treatment schedules; (1) days -3 to 14, (2) days -3 to 3, (3) days 7 to 14 and (4) vehicle. We evaluated the neointimal formation, NADPH oxidase-dependent superoxide production, nitrotyrosine expression and p50 subunit of nuclear factor kappa B (NF-κB p50) expression in balloon-injured and uninjured carotid arteries. Results: In vehicle-treated rats, a significant neointimal formation was observed at 14 days after balloon injury in the carotid artery, and NADPH oxidase-dependent superoxide production, nitrotyrosine expression and NF-κB p50 expression in injured right carotid arteries significantly increased at 2 days after balloon injury as compared with uninjured left carotid arteries. The long-term treatment (initiated 3 days before surgery and continued for 14 days after balloon injury; days -3 to 14) with α-lipoic acid (100 mg/kg/day) markedly reduced the neointimal formation, NADPH oxidase-mediated superoxide production, nitrotyrosine and NF-κB p50 expression. The superoxide production, nitrotyroeine and NF-κB p50 expression at 2 days after balloon injury were significantly inhibited by the short-term treatment with α-lipoic acid (days -3 to 2). The short-term treatment (days -3 to 3) also could suppress the neointimal formation at 14 days after balloon injury. Conclusion: The present study suggests that the treatment with α-lipoic acid leads to a reduction of neointimal formation, probably by inhibiting enhanced superoxide production, nitrotyrosine and NF-κB p50 activation in an early phase after balloon injury.