Correlation of high density lipoprotein (HDL)-associated sphingosine 1-phosphate with serum levels of HDL-cholesterol and apolipoproteins

Background: Extracellular sphingosine 1-phosphate (S1P) has been shown to contribute to the action of high density lipoprotein (HDL) on endothelial and smooth muscle cells. We examined the relationship of lipoprotein-associated S1P concentrations with cholesterol (C) and apolipoprotein (apo) contents of lipoprotein and lipoprotein subfractions characterized by capillary isotachophoresis (cITP). Methods: Blood samples were drawn from 16 volunteers. S1P concentrations were quantified by bioassay based on the ability of S1P to stimulate its receptor. cITP was performed using plasma that had been prestained with NBD-ceramide. Results: In plasma, S1P was concentrated in HDL and associated with LDL at a much lower concentration. HDL–S1P was the major determinant of the plasma S1P concentration. HDL–S1P was strongly and positively (p < 0.001) correlated with serum levels of HDL-C (r = 0.82), apo A-I (r = 0.91) and apo A-II (r = 0.92). HDL–S1P was strongly and positively (p < 0.01) correlated with the apo A-I- and apo A-I/apo A-II-containing cITP HDL subfractions [fast HDL-C (r = 0.66) and intermediate HDL-C (r = 0.80)], but was not significantly correlated with apo E-containing slow HDL, suggesting that S1P is associated with both apo A-I HDL and apo A-I/A-II HDL. LDL–S1P was positively correlated (p < 0.01) with levels of LDL-C (r = 0.65) and apo B (r = 0.85). Conclusion: Lipoprotein-associated S1P was related to the lipoprotein composition of cholesterol and apolipoproteins, suggesting that extracellular S1P may play different roles depending on the particles with which it is associated.