P 46 LXR and ABC-transporter-expression patterns in Trophoblasts in IUGR

Abstract

Introduction Atherogenic lipid oxidation and cholesterol accumulation is increased in the placenta in IUGR. Both, hypoxic conditions and the formation of small molecules like oxysterols however are involved in cellular cholesterol homeostasis by regulating the cholesterol efflux ABC-transporter expression ABCA1 and ABCG1 via activating liver-X-receptors (LXR). Objectives Since it is assumed that hypoxia and oxysterol production or accumulation is increased in the IUGR placenta we questioned whether the LXR-ABCA1 pathway is activated to counteract cholesterol excess. Material and methodes Placentas of 40 IUGR and 40 controls (CTRL) arranged in tissue micro arrays (TMA) were analyzed immunohistochemically for LXRa, LXRb, ABCA1, and ABCG1. The expression was assessed in trophoblasts and endothelium cells semi-quantitatively using Immunoreactivity-Score (IRS). Expression values were related to maternal and fetal lipid profiles. Expression patterns were statistically accomplished via the Mann–Whitney test. Results The LXRa und ABCA1-expression was increased in trophoblasts as compared to controls (LXRa Median IRS (95%CI) IUGR = 6.3 (5.59–7.06), CTRL = 4.8 (4.51–5.85), p = 0.0207; ABCA1 Median IRS (95%CI) IUGR = 7.0 (6.33–7.87), CTRL = 3.9 (3.87–5.67), p = 0.0001). No differences were found in LXRb and ABCG1 expression patterns. Conclusions An increased expression of cholesterol transport molecules in trophoblasts may be a compensatory mechanism against toxic effects of cholesterol excess and oxidation within the placenta.