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Sphingosine 1-phosphate signal survival and mitogenesis are mediated by lipid-stereospecific binding of triacylglycerol-rich lipoproteins
Authors:Y.?M.?Pacheco,R.?Abia,A.?Olivera,S.?Spiegel,V.?Ruiz-Gutierrez,F.?J.?G.?Muriana  author-information"  >  author-information__contact u-icon-before"  >  mailto:muriana@cica.es"   title="  muriana@cica.es"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:(1) Instituto de la Grasa, CSIC, 41012 Seville, Spain;(2) Department of Biochemistry and Molecular Biology, Georgetown University, Medical Center, 20007 Washington DC, USA;(3) Group of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, 41012 Seville, Spain
Abstract:Proof for the role of triacylglycerol-rich lipoproteins (TRLs) in the development of cardiovascular events is accumulating. We recently reported that postprandial TRLs bind to and internalize into human aortic vascular smooth muscle cells (HA-VSMCs) by a lipid-dependent mechanism. We now show that postprandial TRLs triggered hydrolysis of sphingomyelin and stimulation of the sphingosine kinase producing sphingosine 1-phosphate (S1P). In addition, postprandial TRLs exhibited survival and mitogenic effects. Interestingly, the signals were modulated by the nature of the fatty acids located at the sn-2 position in the triacylglycerol molecules of TRL. This lipid-stereospecific regulation of S1P cellular levels in HA-VSMCs provides a novel insight into the intrinsic role of dietary fatty acids and the mechanism mediated by triacylglycerol-containing postprandial lipoproteins in the pathogenesis of atherosclerosis.Received 14 August 2003; received after revision 8 October 2003; accepted 15 October 2003
Keywords:Sphingolipid  VSMC  triacylglycerol-rich lipoprotein  postprandial metabolism
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