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PMID:15793583

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Citation

Wolfrum, C, Poy, MN and Stoffel, M (2005) Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat. Med. 11:418-22

Abstract

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.

Links

PubMed Online version:10.1038/nm1211

Keywords

Animals; Apolipoproteins/physiology; Arteriosclerosis/prevention & control; Cholesterol/metabolism; High-Density Lipoproteins, Pre-beta; Lipoproteins, HDL/biosynthesis; Macrophages/metabolism; Male; Mice; Mice, Inbred C57BL; RNA, Small Interfering; Transfection

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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