β-Carotene and lycopene affect endothelial response to TNF-α reducing nitro-oxidative stress and interaction with monocytes

Scope: Cardiovascular disease (CVD) is associated with vascular oxidative imbalance and inflammation. Increased reactive oxygen species (ROS) generation is associated with a functional inactivation of nitric oxide (NO) due to the reaction with O-2(-), leading to peroxynitrite (ONOO-) formation and subsequent reduction in the beneficial effect of vascular NO bioavailability. Carotenoids'-rich diets have been associated with decreased risk of CVD, but the underlying mechanism is still unknown. Methods and results: In human umbilical vein endothelial cells (HUVECs), both beta-carotene (BC) or lycopene (Lyc) significantly affected tumor necrosis factor-alpha (TNF-alpha)-induced inflammation, being associated with a significant decrease in the generation of ROS (spectrofluorometry) and nitrotyrosine (an index of ONOO- formation, cytofluorimetry), an increased NO/cGMP (cyclic guanosine monophosphate) levels (EIA), and a down-regulation of NF-kappa B-dependent adhesion molecule expression (Western blot and EMSA) and monocyte-HUVEC interaction (adhesion assay). Our results indicate that BC or Lyc treatment reduce the inflammatory response in TNF-alpha-treated HUVECs. This is due to the redox balance protection and to the maintenance of NO bioavailability. Conclusion: Our observations provide background for a novel mechanism for carotenoids' anti-inflammatory activity in the vasculature and may contribute to a better understanding of the protective effects of carotenoid-rich diets against CVD risk.