Sphingosine 1-Phosphate and Apolipoprotein M Levels and Their Correlations with Inflammatory
Biomarkers in Patients with Untreated Familial Hypercholesterolemia
High-density lipoprotein (HDL)-bound apolipoprotein M/sphingosine 1-phosphate (ApoM/S1P)
complex in cardiovascular diseases serves as a bridge between HDL and endothelial
cells, maintaining a healthy endothelial barrier. To date, S1P and ApoM in patients
with untreated heterozygous familial hypercholesterolemia (HeFH) have not been extensively
studied. Eighty-one untreated patients with HeFH and 32 healthy control subjects were
included in this study. Serum S1P, ApoM, sCD40L, sICAM-1, sVCAM-1, oxLDL, and TNFα
concentrations were determined by ELISA. PON1 activities were measured spectrophotometrically.
Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch
Lipid Clinic Network criteria. Significantly higher serum S1P and ApoM levels were
found in HeFH patients compared to controls. S1P negatively correlated with large
HDL and positively with small HDL subfractions in HeFH patients and the whole study
population. S1P showed significant positive correlations with sCD40L and MMP-9 levels
and PON1 arylesterase activity, while we found significant negative correlation between
sVCAM-1 and S1P in HeFH patients. A backward stepwise multiple regression analysis
showed that the best predictors of serum S1P were large HDL subfraction and arylesterase
activity. Higher S1P and ApoM levels and their correlations with HDL subfractions
and inflammatory markers in HeFH patients implied their possible role in endothelial
protection.