Placental expression of adenosine A2A receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system

Kurlak, L.O.; Williams, Paula Juliet; Bulmer, Judith N.; Broughton Pipkin, Fiona; Mistry, Hiten D.

Abstract

Normal placentation occurs under low oxygen tensions yet hypoxia is also implicated in placental pathologies such as pre-eclampsia (PE). Hypoxia-inducible factors (HIFs), adenosine and tissue renin-angiotensin-system (RAS) are known to promote angiogenesis and vascularisation. We hypothesised that placental adenosine A2AR receptor and HIF-1α would change through pregnancy in association with the RAS. Placentae were obtained from women undergoing elective surgical termination of pregnancy (TOP) at ≤10 weeks’ (early TOP) and >10 weeks’ (mid TOP) gestations; at delivery from normotensive (NT) and PE pregnancy. Results were compared to our previously reported data on the angiotensin receptors: AT1R, AT2R and AT4R.
Protein expression of both A2AR and HIF-1α was highest in early TOP and positively correlated through pregnancy (P<0.0001): expression was higher in PE than NT at delivery (P<0.0001 for both). The A2AR positively correlated with the AT4R in placentae in early pregnancy (r=0.53; P=0.035), but not in 3rd trimester samples. Our findings suggest a role for adenosine and RAS in promoting placentation and as a potential adaptation to poor placental perfusion in pre-eclampsia.

Citation

Kurlak, L., Williams, P. J., Bulmer, J. N., Broughton Pipkin, F., & Mistry, H. D. (2015). Placental expression of adenosine A2A receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system. Placenta, 36(5), https://doi.org/10.1016/j.placenta.2015.02.011

• Journal Article Type: Article
• Acceptance Date: Feb 16, 2015
• Online Publication Date: Feb 24, 2015
• Publication Date: May 1, 2015
• Deposit Date: Jul 21, 2017
• Publicly Available Date: Jul 21, 2017
• Journal: Placenta
• Print ISSN: 0143-4004
• Electronic ISSN: 1532-3102
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 5
• DOI: https://doi.org/10.1016/j.placenta.2015.02.011
• Keywords: Placental A2AR; HIF-1α: angiotensin receptors; Early pregnancy; Pre-eclampsia
• Public URL: https://nottingham-repository.worktribe.com/output/983878
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0143400415008103
• Contract Date: Jul 21, 2017