Elevation of circulating Free Fatty Acids (FFAs) has been shown to induce pro-inflammatory changes and oxidative stress. Clinical and experimental studies have shown that high FFAs levels promote endothelial dysfunction, a potential mechanism underlying atherosclerosis and other vascular diseases. As a major component of dietary saturated fat, palmitic acid (PA) is able to induce endothelial dysfunction by redox-sensitive Nf-kB -dependent pathways. The consumption of diets rich in natural bioactive components and their contribution to maintaining or improving cardiovascular health has been a subject of considerable interest to researchers. Anthocyanins, one of the most interesting classes of flavonoids, are widespread in dark red colored fruits and vegetables and seem to play a role in preventing human diseases related to oxidative stress. In this study, primary human umbilical vein endothelial cells (HUVECs) treated with PA were used to explore the protective effects of Cyanidin-3-O-glucoside (C3G), the best-known and investigated anthocyanin, recognized as a potent antioxidant. C3G reduced PA-induced endothelial dysfunction and oxidative stress in HUVECs by reducing Nf-kB activation. In particular, at molecular level, we examined the effects on cellular adaptive response. Our results demonstrated that C3G, also without any kind of stimulus, increased the translocation of the transcription factor Nrf2 into the nucleus so activating antioxidant and detoxifying genes. Furthermore, a crosstalk between Nrf2 and NF-kB pathways has been observed. In fact, Nrf2 inhibited nuclear translocation resulted in NF-kB increase so supporting the molecular mechanism in C3G protective effects. This study demonstrates that C3G is able to protect HUVECs against PA-induced changes in endothelial proatherogenic phenotype, including the activation of NF-kB. This findings might serve as a new therapeutic approach for prevention or treatment of diseases associated with inflammation and oxidative stress. References Steinberg et al. 2003. Vascular function, insulinresistance and fatty acids. Diabetologia , 46, 300−301. Kim et al. Arterioscler Thromb Vasc Biol 2005;25:989-94. Speciale et al Genes Nutr. 2014 Jul;9(4):404
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