Abstract

The fetal umbilical cord blood cholesterol concentration, mainly HDL cholesterol is lower in IUGR neonates as compared to gestational age matched controls (CTRL). One possible explanation is an alteration of cholesterol acceptor concentration or functionality and a disturbed interaction with reverse cholesterol transport (RCT) mechanisms at the placentofetal interface. We aimed to study receptor specific mechanisms of RCT in response to fetal sera of IUGR and CTRL neonates. The cell lines RAW264.7 and HepG2 as well as HUVECs were used to determine the fractional efflux of 3H-cholesterol in response to whole fetal serum (IUGR n = 25; CTRL n = 25) in the absence or presence of ABCA1 overexpression. Efflux values were correlated to serum concentrations of possible cholesterol acceptors like HDL, apoA1, and apoE. Statistics: Wilcoxon rank sum test. Correlation analysis by Spearman’s rank. The main finding was a significant overall reduction of fractional cholesterol efflux in response to IUGR serum as compared to CTRL (p < 0.001). The differences were abolished after overexpression of ABCA1. Cholesterol efflux over all was highly correlated to HDL and ApoE concentration (ρ = 0.777 and ρ = 0.60). The reduced cholesterol efflux acceptor capacity appears to diminish cholesterol availability and transplacental cholesterol transport to fetuses with IUGR. Moreover, disturbances of RCT are critically involved in the pathomechanisms of atherosclerosis. Our results represent a link between the known association of being born small for gestational age and risk of developing cardiovascular diseases later in life. U. Pecks: None. W. Rath: None. S. Hirshman: None. N. Maass: None. D. Schlembach: None. M. Mohaupt: None. G. Escher: None.

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