Acrolein-induced atherogenesis by stimulation of hepatic flavin containing monooxygenase 3 and a protection from hydroxytyrosol.

Abstract

Acrolein, a highly toxic α, β-unsaturated aldehyde, promotes the progression of atherosclerosis in association with inflammatory signaling pathway and reverse cholesterol transport (RCT) process. Additionally, hepatic flavin containing monooxygenase 3 (FMO3) is involved in the pathogenesis of atherosclerosis by regulating cholesterol metabolism. Hydroxytyrosol (HT), as a major phenolic compound in olive oil, exerts anti-inflammatory and anti-atherogenic activities in vitro and animal models. The current study was designed to evaluate whether FMO3 participated in pro-atherogenic process by acrolein and HT showed protective effect during this process. Here, endothelial cells and macrophage Raw264.7 cells were used as the cell models. Following oxidized low-density lipoprotein (OX-LDL) treatment, acrolein exposure promoted foam cells formation in macrophage Raw264.7 cells. The expression of FMO3 and inflammatory makers such as phospho-NF-κB, IL-1β, TNFα as well as IL-6 were significantly increased. However, ATP-binding cassette transporters subfamily A member 1 (ABCA1), a major transporter in RCT process, was repressed by acrolein. In addition, FMO3 knockdown could suppress inflammatory markers and promote ABCA1 expression. Hydroxytyrosol (HT) was observed to reduce lipid accumulation, FMO3 expression as well as inflammatory response. Moreover, it promoted ABCA1 expression. Therefore, our findings indicated that acrolein-enhanced atherogenesis by increasing FMO3 which increased inflammatory responses and decreased ABCA1 in vitro can be alleviated by HT, which may have a therapeutic potential for the treatment of atherosclerosis.