Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.
High-density lipoproteins (HDLs) are considered antiatherogenic because they mediate reverse cholesterol transport from the periphery to the liver for excretion and degradation. Here we show that mice deficient in apolipoprotein M (apoM), a component of the HDL particle, accumulated cholesterol in large HDL particles (HDL(1)) while the conversion of HDL to prebeta-HDL was impaired. Accordingly, apoM-deficient mice lacked prebeta-HDL, a subclass of lipid-poor apolipoproteins that serves as a key acceptor of peripheral cellular cholesterol. This deficiency led to a markedly reduced cholesterol efflux from macrophages to apoM-deficient HDL compared to normal HDL in vitro. Overexpression of apoM in Ldlr(-/-) mice protected against atherosclerosis when the mice were challenged with a cholesterol-enriched diet, showing that apoM is important for the formation of prebeta-HDL and cholesterol efflux to HDL, and thereby inhibits formation of atherosclerotic lesions.
Wolfrum
Christian
C
The Laboratory of Metabolic Diseases, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Poy
Matthew N
MN
Stoffel
Markus
M
D000818:Animals; D001053:Apolipoproteins / Q000502:physiology*; D000075243:Apolipoproteins M; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism*; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D014162:Transfection
C501623:ApoM protein, mouse; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D002784:Cholesterol