Apolipoprotein M promotes cholesterol uptake and efflux from mouse macrophages

Abstract

Apolipoprotein M (ApoM) exhibits various anti-atherosclerotic functions as a component of high-density lipoprotein (HDL) particles. Scavenger receptor class B type I (SR-BI) is a classic HDL receptor that mediates selective cholesterol uptake and enhances the efflux of cellular cholesterol to HDL. However, the effect of ApoM on cholesterol transport in macrophages remains unclear. In this study, we identified for the first time that ApoM is expressed in mouse macrophages and is involved in cholesterol uptake, similar to SR-BI. NBD-cholesterol uptake and efflux in cells were characterized using fluorescence spectrophotometry. The uptake ratios of cholesterol by macrophages from ApoM -/-SR-BI -/mice were significantly lower than those from ApoM +/+ SR-BI -/and ApoM -/-SR-BI +/+ mice. Real-time fluorescence quantitative PCR was used to analyze the expression of cholesterol transport-related genes involved in cholesterol uptake. ApoM-enriched HDL (ApoM + HDL) facilitated more cholesterol efflux from murine macrophage Ana-1 cells than ApoM-free HDL (ApoM -HDL). However, recombinant human ApoM protein inhibited the ability of ApoM -HDL to induce cholesterol efflux. In conclusion, ApoM promotes cholesterol uptake and efflux in mouse macrophages. A better understanding of ApoM function may lead to the development of novel therapeutic strategies for treating atherosclerotic diseases.

Apolipoprotein M and its impact on endothelial dysfunction and inflammation in the cardiovascular system

“…A recent study suggests that apoM is an essential driver for functional cholesterol uptake and efflux in mouse macrophages via SR-BI. Herein, apoM-rich HDL mediated higher cholesterol efflux compared to apoM-deficient HDL [28]. However, the discovery of the apoM/S1P-complex paved the ground for substantial research to use the beneficial properties of S1P-signaling as a potential therapeutic target for CVD.…”

Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases

“…Concordant results were obtained in Apom -deficient mice which present impaired insulin sensitivity, high plasma inflammatory markers such as IL-6 or IL-1β, and hepatic NF-κB [ 99 , 107 ]. Yao et al also recently demonstrated that APOM is expressed in murine and human macrophages, interacts with the scavenger receptor BI to promote cholesterol efflux from the phagocytic cells and protects against atherosclerosis [ 108 , 109 ]. More, Apom -deficient mice display blood hypertension and cardiac hypertrophy compared to wildtype animals [ 110 ].…”