289-POS

Abstract

Objectives Pre-eclampsia (PE) is a serious pregnancy complication which affects 3–5% of the pregnant population. To date there is no ‘cure’ for PE. However, the placenta seems to play an important role in the pathogenesis of this disease. Human placenta is an abundant source of proteoglycans to which glycosaminoglycan (GAG) side chains are attached. Heparan sulphate proteoglycans (HSPGs) have been implicated in many biological processes including, anticoagulation, angiogenesis and inflammation. However, their role in human placentae is largely unknown. The aim of this study was to determine the mRNA expression and protein abundance of HSPGs as well as the structure and relative abundance of GAGs in PE-affected placentae compared to gestation-matched controls. Methods The mRNA expression of HSPGs was determined using real-time PCR. Proteoglycans (PGs) were isolated from placental tissue by anion-exchange chromatography. PG enriched samples were investigated using ELISA with antibodies against the protein core of a range of PGs, as well as GAG chains, and Heparan Sulphate (HS) linkage regions following 0.01 U/mL heparinase III digestion. Results The mRNA expression of HSPGS, syndecan 1 & 2, glypican 1 & 3 and perlecan was significantly reduced in PE-affected placentae compared to controls ( p n = 40 each, Mann–Whitney U test). Syndecans1-4, glypicans1 & 3, biglycan, decorin and perlecan were identified in placental tissues by ELISA following anion exchange chromatography. HS abundance was further investigated using ELISA following digestion with heparinase III to reveal the HS linkage region common to all HS and heparin chains. In PE-affected placentae there was significantly less HS linkage regions compared to controls (1.53 ± 0.0.19 vs 1.03 ± 0.11, n = 20 each, p = 0.0391, Mann–Whitney U test). This correlated with the reduction in HSPG mRNA expression. Conclusions It is plausible that the reduction in PG expression and HS abundance may contribute to the pathogenesis of PE by altering thrombin management or angiogenic and inflammatory processes within the placenta. Disclosures T. Gunatillake: None. A. Chui: None. M. Lord: None. J. Whitelock: None. P. Murthi: None. V. Ignatovic: None. P. Monagle: None. S. Brennecke: None. J. Said: None.