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TY - JOUR AU - Wolfrum, Christian AU - Poy, Matthew N AU - Stoffel, Markus PY - 2005 DA - 2005/04/01 TI - Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis JO - Nature Medicine SP - 418 EP - 422 VL - 11 IS - 4 AB - 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. SN - 1546-170X UR - https://doi.org/10.1038/nm1211 DO - 10.1038/nm1211 ID - Wolfrum2005 ER -