Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Amraoui, F.; Hassani Lahsinoui, H.; Boussata, S.; Keijser, R.; Veenboer, G.J.M.; Middeldorp, S.; van der Post, J.A.M.; Ris-Stalpers, C.; Afink, G.B.; van den Born, B.J.H.
• Is Part Of: Placenta. Volume 36:Issue 11(2015:Nov.)
• Page Start: 1218
• Page End: 1224
• Publication Date: 2015-11
• Subjects: Pre-eclampsia -- Heparan sulfate -- 3-O-Sulfotransferase-3A1 -- Glycocalyx -- Blood pressure -- Birth weight; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2015.09.008
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women. Methods: We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples. Results: Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%–41%) in placental tissue obtained from pre-eclamptic compared to normotensive women ( p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02). Conclusions: The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction. Highlights: Placental mRNA expression of HS3ST3A1 is decreased in pre-eclampsia. Placental mRNA expression of HS3ST3A1 is correlated with maternal blood pressure. Placental mRNA expression of HS3ST3A1 is correlated with birth weight.