Abstract 10028: Overexpression of Stearoyl-Coenzyme A Desaturase 1 in Macrophages Enhanced Macrophage Reverse Cholesterol Transport

Abstract

Stearoyl-coenzyme A desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. However, the impact of SCD1 on atherosclerosis remains unclear. The aim of this study was to determine whether SCD1 affects macrophages reverse cholesterol transport (RCT). Adenoviral-mediated SCD1 overexpression in RAW264.7 macrophages led to increased cholesterol efflux to HDL, but not to apoA-I, compared to the control (luciferase, Luc). There were no differences in ABCA1, ABCG1 and SR-BI expression between the macrophages overexpressing SCD1 and control. While knockdown of ABCG1 and SR-BI also did not affect the SCD1-induced cholesterol efflux to HDL, SCD1-overexpressing macrophages promoted the formation of both normal- and large-sized HDL in media (Figure A), accompanying increased apolipoprotein A-I levels in HDL fractions. Transformation to larger particles of HDL was independently confirmed by nuclear magnetic resonance-based lipoprotein analysis. Interestingly, media transfer assay revealed that HDL generated by SCD1 had the enhanced cholesterol efflux potential. To measure macrophage RCT in vivo, ³H-cholesterol-labeled RAW264.7 macrophages overexpressing SCD1 or control were intraperitoneally injected into wild-type mice. Supporting in vitro data, appearance of ³H-tracer increased in plasma, liver, and feces in mice injected with SCD1-macrophages compared to the control (Figure B-D). Moreover, kinetic studies demonstrated that SCD1 overexpression in the macrophages did not affect the excretion of cholesterol ester from plasma HDL to feces. In summary, these results indicate that overexpression of SCD1 in macrophages promotes in vivo macrophage RCT through increased HDL-mediated cholesterol efflux.