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S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease.

Argraves KM, Sethi AA, Gazzolo PJ, Wilkerson BA, Remaley AT, Tybjaerg-Hansen A, Nordestgaard BG, Yeatts SD, Nicholas KS, Barth JL, Argraves WS - Lipids Health Dis (2011)

Bottom Line: Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo.The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD.These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA. argravek@musc.edu

ABSTRACT

Background: The lysosphingolipid sphingosine 1-phosphate (S1P) is carried in the blood in association with lipoproteins, predominantly high density lipoproteins (HDL). Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo.

Methods: Here we have evaluated how levels of S1P and related sphingolipids in an HDL-containing fraction of human serum correlate with occurrence of ischemic heart disease (IHD). To accomplish this we used liquid chromatography-mass spectrometry to measure S1P levels in the HDL-containing fraction of serum (depleted of LDL and VLDL) from 204 subjects in the Copenhagen City Heart Study (CCHS). The study group consisted of individuals having high serum HDL cholesterol (HDL-C) (females:≥ 73.5 mg/dL; males:≥ 61.9 mg/dL) and verified IHD; subjects with high HDL-C and no IHD; individuals with low HDL-C (females:≤ 38.7 mg/dL; males:≤ 34.1 mg/dL) and IHD, and subjects with low HDL-C and no IHD.

Results: The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD. Furthermore, an inverse relationship with IHD was also observed for two other sphingolipids, dihydro-S1P and C24:1-ceramide, in the HDL-containing fraction of serum. Additionally, we demonstrated that the amount of S1P on HDL correlates with the magnitude of HDL-induced endothelial cell barrier signaling.

Conclusions: These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD.

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Receiver operating characteristic (ROC) curves for the ability of S1P and DH-S1P to distinguish between subjects with and without IHD. Smaller values of the corresponding measure indicate stronger evidence for the presence of IHD. ROC curves were constructed using SPSS v16.
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Figure 2: Receiver operating characteristic (ROC) curves for the ability of S1P and DH-S1P to distinguish between subjects with and without IHD. Smaller values of the corresponding measure indicate stronger evidence for the presence of IHD. ROC curves were constructed using SPSS v16.

Mentions: The ability to correctly classify patients with and without IHD by using levels of S1P and DH-S1P was assessed by receiver operating characteristic (ROC) analysis (Figure 2). S1P and DH-S1P levels in the HDL-containing fraction were both found to discriminate subjects with IHD from those without IHD better than would be expected by chance alone, as characterized by the area under the curves (0.756 for S1P and 0.773 for DH-S1P) (Figure 2).


S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease.

Argraves KM, Sethi AA, Gazzolo PJ, Wilkerson BA, Remaley AT, Tybjaerg-Hansen A, Nordestgaard BG, Yeatts SD, Nicholas KS, Barth JL, Argraves WS - Lipids Health Dis (2011)

Receiver operating characteristic (ROC) curves for the ability of S1P and DH-S1P to distinguish between subjects with and without IHD. Smaller values of the corresponding measure indicate stronger evidence for the presence of IHD. ROC curves were constructed using SPSS v16.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3116499&req=5

Figure 2: Receiver operating characteristic (ROC) curves for the ability of S1P and DH-S1P to distinguish between subjects with and without IHD. Smaller values of the corresponding measure indicate stronger evidence for the presence of IHD. ROC curves were constructed using SPSS v16.
Mentions: The ability to correctly classify patients with and without IHD by using levels of S1P and DH-S1P was assessed by receiver operating characteristic (ROC) analysis (Figure 2). S1P and DH-S1P levels in the HDL-containing fraction were both found to discriminate subjects with IHD from those without IHD better than would be expected by chance alone, as characterized by the area under the curves (0.756 for S1P and 0.773 for DH-S1P) (Figure 2).

Bottom Line: Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo.The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD.These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA. argravek@musc.edu

ABSTRACT

Background: The lysosphingolipid sphingosine 1-phosphate (S1P) is carried in the blood in association with lipoproteins, predominantly high density lipoproteins (HDL). Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo.

Methods: Here we have evaluated how levels of S1P and related sphingolipids in an HDL-containing fraction of human serum correlate with occurrence of ischemic heart disease (IHD). To accomplish this we used liquid chromatography-mass spectrometry to measure S1P levels in the HDL-containing fraction of serum (depleted of LDL and VLDL) from 204 subjects in the Copenhagen City Heart Study (CCHS). The study group consisted of individuals having high serum HDL cholesterol (HDL-C) (females:≥ 73.5 mg/dL; males:≥ 61.9 mg/dL) and verified IHD; subjects with high HDL-C and no IHD; individuals with low HDL-C (females:≤ 38.7 mg/dL; males:≤ 34.1 mg/dL) and IHD, and subjects with low HDL-C and no IHD.

Results: The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD. Furthermore, an inverse relationship with IHD was also observed for two other sphingolipids, dihydro-S1P and C24:1-ceramide, in the HDL-containing fraction of serum. Additionally, we demonstrated that the amount of S1P on HDL correlates with the magnitude of HDL-induced endothelial cell barrier signaling.

Conclusions: These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD.

Show MeSH
Related in: MedlinePlus