Protective effects of chronic resveratrol treatment on vascular inflammatory injury in streptozotocin-induced type 2 diabetic rats: Role of NF-kappa B signaling

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of macrovascular disease. Epidemiological studies suggest that plant polyphenol resveratrol (REV) is associated with reduced risk of cardiovascular diseases. Since chronic inflammatory and endothelial cell activation play a critical role in vascular aging and atherogenesis, we evaluated whether REV can inhibit inflammatory-induced vascular injury in T2DM. We found that REV (50 mg/kg/d) can regulate glucose and lipid metabolism, improve insulin resistance and vascular permeability, and protect against the foam cells and cholesterol crystals formation in arterial vessel walls of T2DM rats. The protective effects of REV were consistent with the decrease in nuclear translocation of nuclear factor kappa B (NF-kappa B) and the down-regulation of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levers in blood and tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) expressions in vascular wall. In addition, REV (10 and 100 nmol/L) treatment protected cultured endothelial cells against increases in the expression of TNF-alpha, ICAM-1, and MCP-1 mRNA and protein induced by high glucose via inhibiting nuclear translocation of NF-kappa B p65. The specific NF-kappa B inhibitor pyrrolidine dithiocarbamate- (PDTC-) or small interfering RNA directed against NF-kappa B p65-mediated downregulation of NE-kappa B p65 was further enhanced by REV (100 nmol/L) in the human endothelial cell line EA.hy926. In conclusion, these observations suggest that chronic treatment of T2DM rats with REV attenuates the inflammatory injury of the vascular wall and the effects are associated with down-regulation of the NF-kappa B signal pathway. (C) 2013 Elsevier B.V. All rights reserved.