Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis
Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis
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DOI：
10.1038/nm1211
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发表时间：
2005-04-01
期刊：
影响因子：
82.9
通讯作者：
Stoffel, M
中科院分区：
文献类型：
--
作者：
Wolfrum, C;Poy, MN;Stoffel, M
高密度脂蛋白（HDL）被认为是抗动脉粥样硬化的，因为它们介导胆固醇从外周逆向转运到肝脏进行排泄和降解。在这里，我们表明，载脂蛋白M（apoM），HDL颗粒的一个组成部分，小鼠缺乏，积累胆固醇在大HDL颗粒（HDL 1），而HDL的前β-HDL的转化受损。因此，apoM缺陷小鼠缺乏前β-HDL，这是一种作为外周细胞胆固醇关键受体的贫脂载脂蛋白亚类。这种缺陷导致了显着减少胆固醇流出巨噬细胞apoM缺陷HDL相比，正常的HDL在体外。在Ldlr（-/-）小鼠中apoM的过表达在用富含胆固醇的饮食攻击小鼠时保护小鼠免受动脉粥样硬化，表明apoM对于前HDL的形成和胆固醇流出到HDL是重要的，从而抑制动脉粥样硬化病变的形成。
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 pre beta-HDL was impaired. Accordingly, apoM-deficient mice lacked pre beta-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 pre-HDL and cholesterol efflux to HDL, and thereby inhibits formation of atherosclerotic lesions.