Sphingosine 1-phosphate signal survival and mitogenesis are mediated by lipid-stereospecific binding of triacylglycerol-rich lipoproteins

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