Abstract 457: Sulforaphane at Physiological Concentrations Inhibits TNF-α-Induced Monocyte Adhesion to Human Vascular Endothelial Cells and Improves Vascular Inflammation in Mice Through a Nuclear Factor-κB--Mediated Mechanism

Introduction: TNF-α, plays an important role in endothelial dysfunction and is involved in the pathogenesis of atherosclerosis. Aim: We investigated the protective effect of cruciferous vegetable phytochemical sulforaphane at physiological concentrations on TNF-α-induced vascular inflammation. Methods: Human umbilical vascular endothelial cells (HUVEC) were pretreated with sulforaphane (0.5 - 8 μM) before addition of TNF-α for 6 h. Cell adhesion was measured with calcein-AM labeled human monocytes. In animal study, ten weeks old male C57BL/6 mice were fed a diet containing 0 or 300 ppm sulforaphane for 2 weeks followed by TNF-α administration. The chemokines and adhesion molecules in the serum were measured using ELISA Kit. VCAM-1 and F4/80 expressions in mice aorta were performed using immunohistochemistry. Results: Sulforaphane at physiological concentrations (0.5 - 2 μM) significantly inhibited TNF-α-induced adhesion of monocytes to HUVECs and suppressed TNF-α-induced production of monocyte chemoattractant protein -1 (MCP-1) and interleukin-8 (IL-8). Furthermore, sulforaphane inhibited TNF-α-induced NF-κB transcriptional activity, IκBα degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit endothelial inflammation by suppressing NF-κB signaling. In animal study, dietary sulforaphane (300 ppm in the diet) significantly suppressed TNF-α-induced increase in circulating chemokines and adhesion molecules in C57BL/6 mice. Sulforaphane treatment also reduced the presence of VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α treated mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers9 delicate organization as shown by Verhoeff-van Gieson staining. Conclusion: sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway.