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.
Pacheco
Y M
YM
Instituto de la Grasa, CSIC, 41012 Seville, Spain.
Abia
R
R
Olivera
A
A
Spiegel
S
S
Ruiz-Gutierrez
V
V
Muriana
F J G
FJ
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008246:Lysophospholipids; D008938:Mitosis / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*; D000099157:Sphingosine Kinase
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D008074:Lipoproteins; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D043562:Receptors, G-Protein-Coupled; D013109:Sphingomyelins; D013110:Sphingosine; D014280:Triglycerides; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate