Predicting obstructive coronary artery disease with serum sphingosine-1-phosphate

Deutschman, Douglas H.; Carstens, Jeffrey S; Klepper, Robert L; Smith, Wyatt S.; Pagé, Maude; T, Young; Gleason, Lisa A.; Nakajima, Nobuko; Sabbadini, Roger A.

doi:10.1016/s0002-8703(03)00118-2

Cited by 169 publications

(153 citation statements)

References 23 publications

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“…On the one hand, the S1P in HDL has been shown to bind to S1P/Edg receptors on human endothelial cells and, for this reason, probably mediates many of the anti-inflammatory actions of HDL on endothelial cells (34). On the other hand, serum S1P was found to be a remarkably strong predictor of both the occurrence and the severity of coronary stenosis in a recent case-control study (35). It should be noted that the S1P concentration in apoE KO mice is Ͼ200 nM (Table II), and the amount needed to activate S1P receptors on endothelial cells is ϳ100 nM (34,36).…”

Section: Discussionmentioning

confidence: 96%

Effect of Myriocin on Plasma Sphingolipid Metabolism and Atherosclerosis in apoE-deficient Mice

Hojjati

Zhou

et al. 2005

Journal of Biological Chemistry

270

211

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Sphingolipids play a very important role in cell membrane formation, signal transduction, and plasma lipoprotein metabolism, all of which may well have an impact on the development of atherosclerosis. To investigate the relationship between sphingolipid metabolism and atherosclerosis, we utilized myriocin to inhibit mouse serine palmitoyl-CoA transferase (SPT), the key enzyme for sphingolipid biosynthesis. We injected 8-week-old apoE-deficient mice with myriocin (0.3 mg/ kg/every other day, intraperitoneal) for 60 days. On a chow diet, myriocin treatment caused a significant decrease (50%) in liver SPT activity (p < 0.001), significant decreases in plasma sphingomyelin, ceramide, and sphingosine-1-phosphate levels (54, 32, and 73%, respectively) (p < 0.0001), and a significant increase in plasma phosphatidylcholine levels (91%) (p < 0.0001). Plasma total cholesterol and triglyceride levels demonstrated no significant changes, but there was a significant decrease in atherosclerotic lesion area (42% in root and 36% in en face assays) (p < 0.01). On a high fat diet, myriocin treatment caused marked decreases in plasma sphingomyelin, ceramide, and sphingosine-1-phosphate levels (59, 66, and 81%, respectively) (p < 0.0001), and a marked increase in plasma phosphatidylcholine levels (100%) (p < 0.0001). Total cholesterol and triglyceride demonstrated no significant changes, but there was a significant decrease in atherosclerotic lesion area (39% in root and 37% in en face assays) (p < 0.01). These results indicate that, apart from cholesterol levels, sphingolipids have an effect on atherosclerotic development and that SPT has proatherogenic properties. Thus, inhibition of SPT activity could be an alternative treatment for atherosclerosis.Sphingolipids have many biological functions, including cell membrane formation, signal transduction, and lipid metabolism, and all of these may be related to the development of atherosclerosis. Serine palmitoyl-CoA transferase (SPT) 1 is the rate-limiting enzyme in the biosynthesis of sphingolipids (1). It has long been known that SPT plays an important role in the metabolism of sphingolipids, but its role in other lipid metabolisms and atherosclerosis has not been unequivocally determined. When SPT activity is increased in rat liver (2) and lung (3), sphingolipid formation is likewise increased. The activity of SPT is heightened in the aortas of rabbits fed a high cholesterol diet (4). Two candidate cDNAs for yeast SPT, termed LCB1 and LCB2, have been cloned (5, 6), and the translated sequences indicate that their gene products have a 21% amino acid sequence identity (6). The lack of SPT activity in a yeast strain defective in LCB1 or LCB2, together with the protein similarity data, suggest that the two genes encode subunits of SPT (6). Mouse and human LCB1 and LCB2 cDNA homologues have also been cloned (7,8). In mouse, the two mRNAs have the same tissue distribution (lung, kidney Ͼ brain Ͼ cartilage, skin Ͼ heart Ͼ liver Ͼ muscle), and the ratio of the amounts of the two transcri...

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Section: Discussionmentioning

confidence: 96%

Effect of Myriocin on Plasma Sphingolipid Metabolism and Atherosclerosis in apoE-deficient Mice

Hojjati

Zhou

et al. 2005

Journal of Biological Chemistry

270

211

View full text Add to dashboard Cite

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“…Furthermore, Deutschman et al. (2003) found an association between serum S1P concentration and severity of stenosis in CAD patients undergoing coronary angiography. Contrary to these findings, Argraves et al.…”

Section: Introductionmentioning

confidence: 99%

Plasma sphingolipids and depressive symptoms in coronary artery disease

et al. 2017

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BackgroundDepression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects.MethodsDepressive symptoms were measured using the depression subscale of the self‐reported Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were measured from fasting plasma samples using high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear regression models were used to assess associations between log‐transformed concentrations of plasma sphingolipids and depressive symptoms.ResultsA total of 111 CAD patients (mean (SD) age = 63.6 ± 6.4, 84.7% male) were included. In linear regression analyses, higher plasma concentrations of ceramides C16:0 (β = 0.204, p = .026) and C18:0 (β = 0.209, p = .023) and sphingomyelin SM18:1 (β = 0.210, p = .024) were significantly associated with higher HADS depression subscale score after adjusting for covariates.ConclusionSphingolipids, in particular the ceramide species C16:0 and C18:0 and the sphingomyelin species SM18:1, may be implicated in the pathophysiology of depression in CAD. The association between plasma sphingolipid concentrations and depression should be further examined in CAD patients and in other populations.

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“…The fact that S1P is a regulatory lipid [42] suggests that its circulating levels may be involved in undetermined processes. While increase in circulating S1P was recently associated with inflammatory coronary artery disease [32] and cancer [34], its sources were unclear. With the baseline levels of circulating S1P being maintained by blood cells [28][29][30][31], it is conceivable that these levels may be altered by various pathological conditions or therapeutic interventions, which may in turn influence homeostasis at distant sites.…”

Section: Discussionmentioning

confidence: 99%

“…The potential of S1P to have a role as a serum marker of human disease has been recently demonstrated in a study which showed that an elevated concentration of S1P in patients' serum was associated with inflammatory coronary artery disease [32]. Circulating levels of S1P were also associated with murine colon cancer [33] or human ovarian cancer (although no difference between stages was observed) [34], and S1P receptor antagonists are in a wide variety of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Circulating sphingosine-1-phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer

Pchejetski

Nunes

Sauer

et al. 2010

Breast Cancer Res Treat

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Predicting obstructive coronary artery disease with serum sphingosine-1-phosphate

Cited by 169 publications

References 23 publications

Effect of Myriocin on Plasma Sphingolipid Metabolism and Atherosclerosis in apoE-deficient Mice

Effect of Myriocin on Plasma Sphingolipid Metabolism and Atherosclerosis in apoE-deficient Mice

Plasma sphingolipids and depressive symptoms in coronary artery disease

Circulating sphingosine-1-phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer

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