Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 14, Issue 3, Pages 4419-4431Publisher
MDPI AG
DOI: 10.3390/ijms14034419
Keywords
apolipoprotein M; sphingosine-1-phosphate; atherosclerosis; lipoprotein metabolism
Funding
- Danish Research Council
- General Secretariat of Research and Technology of Greece
- The University of Copenhagen, Denmark
- Established Investigator of the Netherlands Heart Foundation [2009T038]
- Lundbeck Foundation [R126-2012-12400] Funding Source: researchfish
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Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM was identified as a carrier of the bioactive lipid sphingosine-1-phosphate (S1P). S1P activates five different G-protein-coupled receptors, known as the S1P-receptors 1-5 and, hence, affects a wide range of biological processes, such as lymphocyte trafficking, angiogenesis, wound repair and even virus suppression and cancer. The ability of apoM to bind S1P is due to a lipophilic binding pocket within the lipocalin structure of the apoM molecule. Mice overexpressing apoM have increased plasma S1P concentrations, whereas apoM-deficient mice have decreased S1P levels. ApoM-S1P is able to activate the S1P-receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM-S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis.
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