Resveratrol attenuates TNFalfa‐induced activation of coronary arterial endothelial cells: role of NF‐kB inhibition

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its cardioprotective effects are not completely understood. Because TNFalfa‐induced endothelial activation and vascular inflammation plays a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits TNFalfa‐induced signal transduction in human coronary arterial endothelial cells (HCAECs). TNFalfa significantly increased adhesiveness of the monocytic THP‐1 cells to HCAECs, an effect that could be inhibited by resveratrol and the NF‐kB inhibitor PDTC. TNFalfa‐induced endothelial activation was prevented by the NAD(P)H oxidase inhibitor apocynin or catalase plus SOD. Resveratrol also inhibited H2O2–induced monocyte adhesiveness. Using a reporter gene assay we found that in HCAECs TNFalfa significantly increased NF‐kB activity, which could be inhibited by resveratrol (>50% inhibition at 10‐6 mol/L) and PDTC. Resveratrol also inhibited TNFalfa‐induced, NF‐kB‐driven luciferase expression in rat aortas electroporated with the reporter gene construct. In TNFalfa‐treated HCAECs resveratrol attenuated expression of NF‐kB‐dependent inflammatory markers iNOS, IL‐6, BMP‐2, ICAM‐1 and VCAM. Thus, resveratrol at nutritionally relevant concentrations inhibits TNFalfa‐induced NF‐kB activation and inflammatory gene expression and attenuates monocyte adhesiveness to HCAECs. We propose that these anti‐inflammatory actions of resveratrol are responsible, at least in part, for its cardioprotective effects. (Grant support: AHA 0430108N, 0435140N, NIH HL077256, Philip Morris USA).