Dose-dependent effect of Resveratrol on human endothelial cell functions

Purpose - Resveratrol consumption has been shown to exhibit cardiovascular-preventive and anticancer activities in preclinical studies. The mechanism of Resveratrol effect on human umbilical vein endothelial cell proliferation and apoptosis were not clearly understood. This study was undertaken to study on the dose-dependent effect of Resveratrol on HUVEC function and identify the potential signals involved in this pathway.Experimental Design and Results - HUVECs were used as described in this study. Treatment of HUVECs with the concentrations of 1 and 100 µM RES showed that low concentrations increase cell growth, and decrease intracellular ROS levels while high concentrations cause the opposite effect significantly. The result of DNA fragmentation experiments may indicate cell death by apoptosis in HUVECs related to the expression of Bax and the decrease of the expression of Bcl-2. Using RES 50 μM, is consistent with the significant increase in DNA fragmentation, a typical marker of apoptosis. And at this concentration, RES makes endothelial cell cycle arrest by reducing Cyclin D1 and ODC, c-myc expression. Resveratrol dose-dependently modulates PKC activity on HUVEC proliferation and apoptosis.Conclusion - Our data indicated that the RES effect on HUVECs is biphasic. PKC appears to be the potential mediator of the observed Resveratrol effect on HUVEC functions (proliferation, apoptosis), hypothesized this linked to the intracellular ROS levels.