Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

Area of Science:

• Lipid Metabolism
• Cardiovascular Research
• Apolipoprotein Biology

Background:

• Apolipoprotein M (apoM) is associated with high-density lipoprotein (HDL) and shows protective effects against atherosclerosis.
• The precise mechanism by which apoM exerts its atheroprotective effects remains unclear.
• ApoM is known to promote the formation of prebeta-HDL particles.

Purpose of the Study:

• To investigate the role of plasma apolipoprotein M (apoM) in the mobilization of cholesterol from peripheral cells in a mouse model.
• To determine if apoM influences cholesterol efflux from macrophages and overall cholesterol transport in vivo.

Main Methods:

• Assessed in vitro cholesterol efflux from macrophages using HDL from apoM-transgenic and wild-type (WT) mice.
• Evaluated in vivo cholesterol mobilization from implanted foam cells in apoM-/-, WT, and apoM-transgenic mice.
• Measured cholesterol flux into plasma using stable isotope labeling (13C2-cholesterol) during constant intravenous infusion.

Main Results:

• HDL enriched with apoM significantly increased in vitro cholesterol efflux from macrophages compared to WT HDL.
• In vivo studies showed a trend towards increased cellular cholesterol mobilization to plasma with higher plasma apoM levels, but no effect on fecal excretion.
• Mice with higher plasma apoM levels exhibited a significantly lower rate of enrichment of blood free cholesterol, indicating increased flux of unlabeled cholesterol into plasma.

Conclusions:

• Plasma apoM levels play a role in modulating the capacity of plasma to mobilize cholesterol from peripheral cells.
• ApoM does not appear to have a significant influence on the fecal excretion of cholesterol.
• These findings suggest a mechanism for apoM's atheroprotective role involving enhanced cellular cholesterol efflux.