4.7 Article

Sphingosine 1-Phosphate and Apolipoprotein M Levels and Their Correlations with Inflammatory Biomarkers in Patients with Untreated Familial Hypercholesterolemia

Journal

Publisher

MDPI
DOI: 10.3390/ijms232214065

Keywords

sphingosine 1-phosphate; apolipoprotein M; familial hypercholesterolemia; sCD40 ligand; soluble vascular adhesion molecule-1; arylesterase activity; high-density lipoprotein; inflammation

Funding

  1. National Research, Development and Innovation Office-NKFIH [K142273, TKP2021-EGA-18]
  2. Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, under the TKP2021-EGA funding scheme
  3. Eotvos Lorand Research Network [11003]

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In untreated patients with HeFH, elevated levels of serum S1P and ApoM showed correlations with HDL subfractions and inflammatory markers, suggesting their possible role in endothelial protection.
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 TNF alpha 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.

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