Abstract
BackgroundThe oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Pregnancy pathologies like preeclampsia (PE), HELLP-syndrome (HELLP), intrauterine growth restriction (IUGR) and intrahepatic cholestasis in pregnancy (ICP) are linked to disturbances in lipid metabolism. In the present study, we hypothesized a specific gestational regulation of 27-OHC and compromised 27-OHC levels due to placental and hepatic diseases in pregnancy resulting in a dysregulation of lipid metabolism.MethodsThe 27-OHC was measured by gas-chromatography-mass spectrometry (GC-MS) and related to cholesterol concentrations. In the longitudinal cohort, a complete set of samples of healthy patients (n = 33) obtained at three different time points throughout gestation and once post-partum was analyzed. In the cross sectional cohort, patients with pregnancy pathologies (IUGR n = 14, PE n = 14, HELLP n = 7, ICP n = 7) were matched to a control group (CTRL) of equal gestational ages.ResultsThe 27-OHC levels already increased in the first trimester despite lower TC concentrations (p < 0.05). During the course of pregnancy, a subtle rise in 27-OHC concentrations results in an overall decrease of 27-OHC/TC ratio in between the first (p < 0.05) and second trimester. The ratio remains stable thereafter including the post-partum period. No significant differences have been observed in pregnancy pathologies as compared to the CTRL group.ConclusionIn conclusion, 27-OHC may have a compensatory role in cholesterol metabolism early in pregnancy. The conserved 27-OHC/TC ratio in pregnancy pathologies suggest that neither the placenta nor the liver is majorly involved in the regulation of 27-OHC metabolism.
Highlights
The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis
We found a tendency of higher TG values (+43%) in the PE group in comparison to control group (CTRL)
The changes in 27-OHC are not exactly parallel to those found in total cholesterol concentrations (TC), as indicated by the 27-OHC/TC ratio. 27OHC concentrations are relatively higher than TC in first trimester samples, while in later phases of gestation and p.p. both cholesterol levels were parallel to each other
Summary
The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Oxysterols are mono-oxygenated metabolites of cholesterol and play an important role in the regulation and maintenance of whole-body cholesterol homeostasis. They participate in different aspects of lipid metabolism and have been ascribed a number of roles in connection with atherosclerosis, inflammation, apoptosis and immunosuppression [6, 7]. 27-hydroxycholesterol (27-OHC) is the quantitatively most dominating oxysterol in the circulation of human adults [8]. It is produced upon hydroxylation of cholesterol by the enzyme sterol 27-hydroxylase (CYP27A1) [9]. Loss of function mutation in CYP27A1 leads to Cerebrotendinous Xanthomatosis, a disease characterized by the absence of 27-OHC and associated to early onset of atherosclerosis, despite normal circulating plasma cholesterol concentrations
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