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

Christian Wolfrum, Matthew N. Poy, Markus Stoffel

Research output: Contribution to journalArticle

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 apolipoproiein 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.

Original languageEnglish (US)
Pages (from-to)418-422
Number of pages5
JournalNature medicine
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Apolipoprotein M is required for preβ-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis'. Together they form a unique fingerprint.

  • Cite this