Astaxanthin Decreases Inflammatory Biomarkers Associated with Cardiovascular Disease in Human Umbilical Vein Endothelial Cells

Abstract

Oxidative stress and inflammation are strongly linked to the development of cardiovascular disease (CVD). As a potent antioxidant, astaxanthin may downregulate inflammation-associated factors involved in endothelial dysfunction and CVD progression. We studied the possible protective effects of astaxanthin against endothelial dysfunction in human umbilical vein endothelial cells (HUVEC) induced with hydrogen peroxide (H2O2). Cells were pre-incubated with 0, 0.01, 0.1, or 1.0 μmol/L astaxanthin for 48 h, then oxidative stress induced with 100 μmol/L H2O2 overnight. Uptake kinetics of astaxanthin showed a time-dependent uptake of astaxanthin (1.0 μmol/L) by HUVEC over the 48 h incubation period. Oxidative stress induction with H2O2 in HUVEC decreased intracellular antioxidant activity and increased the production of inflammatory biomarkers and reactive oxygen species (ROS). In contrast, pre-incubation of HUVEC with astaxanthin prior to H2O2 stress increased (P < 0.05) superoxide dismutase activity and decreased ROS, prostaglandin E2, leukotriene B4, NO, IL-8, and IFN- production. Pre-treatment with astaxanthin also downregulated the transcriptional activation of NF-κB and activator protein-1, thereby inhibiting downstream production of inflammatory mediators and cytokines. Therefore, astaxanthin protects against factors initiated by H2O2 addition, likely by scavenging ROS required for transcriptional activation and inhibiting the production of inflammatory biomarkers involved in endothelial dysfunction and CVD. Abbreviations: AP-1: activator protein-1; CVD: cardiovascular disease; CS: culture supernatant; EGM-2: endothelial growth medium-2; GPx: glutathione peroxidase; H2O2: hydrogen peroxide; HUVEC: human umbilical vein endothelial cell; LTB4: leukotriene B4; PGE2: prostaglandin E2; ROS: reactive oxygen species; SOD: superoxide dismutase; THF: tetrahydrofuran.