Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis

被引:0
|
作者
Christian Wolfrum
Matthew N Poy
Markus Stoffel
机构
[1] The Laboratory of Metabolic Diseases,
[2] The Rockefeller University,undefined
来源
Nature Medicine | 2005年 / 11卷
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摘要
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 (HDL1) while the conversion of HDL to preβ-HDL was impaired. Accordingly, apoM-deficient mice lacked preβ-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 preβ-HDL and cholesterol efflux to HDL, and thereby inhibits formation of atherosclerotic lesions.
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页码:418 / 422
页数:4
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