Resveratrol Attenuates Oxidative Stress Induced by Balloon Injury in the Rat Carotid Artery Through Actions on the ERK1/2 and NF-Kappa B Pathway

Background/Aim: Oxidative stress plays a critical role in pathogenesis of the neointimal arterial hyperplasia. The aim of the study was to evaluate effects of resveratrol (RSV) on the vascular hyperplasia stimulated by oxidative damage. Methods: Balloon vascular injury was induced in rats that were intraperitonealy exposed to resveratrol (1 mg/kg) on 7 or 14 days after surgical procedure. Animals were euthanized on 7 or 14 days after operation. The blood level of 8-iso-prostaglandin F2 alpha, arterial morphology as well as expression of monocyte chemotactic protein-1 and interleukin-6 in carotid wall were measured. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta. Cellular proliferation and migration assays, reactive oxygen species (ROS), superoxide dismutase (SOD) and NADPH oxidative activity, protein level of beta-actin, histone H3, NF-kappa B p65, I kappa B, ERK1/2, phospho-ERK1/2, phospho-p38 as well as NF-kappa B transcription activity were evaluated in-vitro after angiotensin II stimulation and resveratrol (50-200 mu mol/L) treatment. Results: Significant decreases in neointimal/medial area, serum prostaglandin level and genes expression were found in rats treated with resveratrol, when compared to the control group. Significant changes were also revealed for proliferation and migration rates, ROS level, as well as SOD, NADPH oxidase, ERK1/2 phosphorylation and NF-kappa B transcriptional activity in cell cultures exposed to highest dose of resveratrol. Insignificant changes were observed for NF-kappaB p65 translocation and I kappa B degradation, p38 phosphorylation in MAPK pathway. Conclusion: Resveratrol significantly suppressed the neointimal hyperplasia after balloon injury through inhibition of oxidative stress and inflammation by blocking the ERK1/2/NF-kappa B pathway. Copyright (C) 2013 S. Karger AG, Basel