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Atherosclerosis. 2011 Dec;219(2):855-63. doi: 10.1016/j.atherosclerosis.2011.08.049. Epub 2011 Sep 6.

Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism.

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  • 1Institute of Clinical Chemistry, University and University Hospital Zurich, Switzerland.

Abstract

BACKGROUND:

Apolipoprotein M (apoM) has been identified as a specific sphingosine-1-phosphate (S1P) binding protein of HDL.

OBJECTIVES AND METHODS:

To investigate the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as 50 patients with seven different monogenic disorders of HDL metabolism and their 51 unaffected relatives.

RESULTS:

Compared to wild type mice, S1P plasma levels in apoM knock-out and apoM transgenic mice were decreased by 30% and increased by 270%, respectively. Compared to family controls, S1P and apoM levels in apoB-depleted plasma were significantly decreased by in average 34% and 12%, respectively, in heterozygous carriers of mutations in APOA1, LCAT or ABCA1, and by 70% and 48%, respectively, in carriers of two defective alleles in LCAT or ABCA1. Heterozygous mutations in CETP, SCARB1, LIPC, or LIPG did not significantly affect S1P or apoM concentrations. Albumin-corrected molar S1P-to-apoM ratios varied from 0.12 to 0.8 (median 0.3) and were not affected by any mutation. S1P levels in apoB-depleted plasma correlated significantly with HDL-cholesterol and less so with apoM both if apoA-I plasma concentrations were below the median.

CONCLUSION:

In the context of previous data, our findings can be explained by the existence of a specific apoM and S1P containing HDL subclass which contains a considerable molar excess of apoM over S1P and is critically determined by apoA-I up to a threshold concentration around the median found in a Caucasian population.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
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