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The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis
Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden 2300, The Netherlands
Pharmacology Unit, Department of Medicine, University of Patras Medical School, Rio TK. 26500, Greece
Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark
* Author to whom correspondence should be addressed.
Received: 5 December 2012; in revised form: 17 January 2013 / Accepted: 5 February 2013 / Published: 25 February 2013
Abstract: 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.
Keywords: apolipoprotein M; sphingosine-1-phosphate; atherosclerosis; lipoprotein metabolism
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MDPI and ACS Style
Arkensteijn, B.W.C.; Berbée, J.F.P.; Rensen, P.C.N.; Nielsen, L.B.; Christoffersen, C. The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis. Int. J. Mol. Sci. 2013, 14, 4419-4431.
Arkensteijn BWC, Berbée JFP, Rensen PCN, Nielsen LB, Christoffersen C. The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis. International Journal of Molecular Sciences. 2013; 14(3):4419-4431.
Arkensteijn, Bas W.C.; Berbée, Jimmy F.P.; Rensen, Patrick C.N.; Nielsen, Lars B.; Christoffersen, Christina. 2013. "The Apolipoprotein M–Sphingosine-1-Phosphate Axis: Biological Relevance in Lipoprotein Metabolism, Lipid Disorders and Atherosclerosis." Int. J. Mol. Sci. 14, no. 3: 4419-4431.