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Journal of Lipid Research, Vol. 47, 1833-1843, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Isolation and characterization of human apolipoprotein M-containing lipoproteins

Christina Christoffersen^*, Lars Bo Nielsen^*,1, Olof Axler, Astra Andersson, Anders H. Johnsen^* and Björn Dahlbäck^1,

^* Department of Clinical Biochemistry, Rigshospital, University of Copenhagen, Copenhagen DK-2100, Denmark
Department of Laboratory Medicine, Division of Clinical Chemistry, University of Lund, University Hospital, SE-20502 Malmö, Sweden

Published, JLR Papers in Press, May 8, 2006.

¹ To whom correspondence should be addressed. e-mail: larsbo{at}rh.dk (L.B.N.); bjorn.dahlback{at}med.lu.se (B.D.)

Apolipoprotein M (apoM) is a novel apolipoprotein with unknown function. In this study, we established a method for isolating apoM-containing lipoproteins and studied their composition and the effect of apoM on HDL function. ApoM-containing lipoproteins were isolated from human plasma with immunoaffinity chromatography and compared with lipoproteins lacking apoM. The apoM-containing lipoproteins were predominantly of HDL size; 5% of the total HDL population contained apoM. Mass spectrometry showed that the apoM-containing lipoproteins also contained apoJ, apoA-I, apoA-II, apoC-I, apoC-II, apoC-III, paraoxonase 1, and apoB. ApoM-containing HDL (HDL^apoM+) contained significantly more free cholesterol than HDL lacking apoM (HDL^apoM–) (5.9 ± 0.7% vs. 3.2 ± 0.5%; P < 0.005) and was heterogeneous in size with both small and large particles. HDL^apoM+ inhibited Cu²⁺-induced oxidation of LDL and stimulated cholesterol efflux from THP-1 foam cells more efficiently than HDL^apoM–. In conclusion, our results suggest that apoM is associated with a small heterogeneous subpopulation of HDL particles. Nevertheless, apoM designates a subpopulation of HDL that protects LDL against oxidation and stimulates cholesterol efflux more efficiently than HDL lacking apoM.

Abbreviations: apoM, apolipoprotein M; HRP, haptoglobin-related protein; PON1, paraoxonase 1

Supplementary key words cholesterol efflux • oxidation • apoM

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