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The placental renin-angiotensin system and oxidative stress in pre-eclampsia

Mistry, H.D.; Kurlak, L.O.; Broughton Pipkin, Fiona

Authors

H.D. Mistry hiten.mistry@nottingham.ac.uk

L.O. Kurlak lesia.kurlak@nottingham.ac.uk

Fiona Broughton Pipkin



Abstract

There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin receptor (PRR) both enhance the cleavage of angiotensin I from angiotensinogen (AGT). Pre-eclampsia, a hypertensive disorder of pregnancy, manifests as high blood pressure and proteinuria, and is a state of increased oxidative stress.
Objectives, study design and main outcome measures
Hypothesis: Pre-eclampsia will be associated with increased placental expression of components of the renin–angiotensin system, which could result in reduced infant birthweight. Biopsies were taken 1 cm from the placental edge from 27 normotensive controls and 23 pre-eclamptic White European women. Immunohistochemistry was performed for AGT, PRR, glutathione peroxidase 3 (GPx3) and the AT1R and AT2R AngII receptors. Protein expression was semi-quantitatively assessed (H-score).
Results: AT1R expression was significantly increased in pre-eclamptic placentae, and negatively correlated with birthweight (r = −0.529, P = 0.009). AT1R expression was also negatively correlated with GPx3 expression overall (r = −0.647; P = 0.005). AT2R expression positively correlated with AGT (r = 0.615, P = 0.002) in the pre-eclamptic placentae only.
Conclusions: The raised AT1R expression in pre-eclampsia, together with inadequate antioxidant protection, possibly through lower GPx activity, might enhance the vasoconstrictor effect of locally-generated AngII, contributing to the restricted fetal growth characteristic of pre-eclampsia. Conversely, the AT2R:AGT association within the pre-eclamptic placenta may provide a compensatory mechanism.

Citation

Mistry, H., Kurlak, L., & Broughton Pipkin, F. (2013). The placental renin-angiotensin system and oxidative stress in pre-eclampsia. Placenta, 34(2), https://doi.org/10.1016/j.placenta.2012.11.027

Journal Article Type Article
Acceptance Date Nov 26, 2012
Online Publication Date Dec 14, 2012
Publication Date Feb 1, 2013
Deposit Date Jul 19, 2017
Publicly Available Date Jul 19, 2017
Journal Placenta
Print ISSN 0143-4004
Electronic ISSN 1532-3102
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 34
Issue 2
DOI https://doi.org/10.1016/j.placenta.2012.11.027
Public URL http://eprints.nottingham.ac.uk/id/eprint/44270
Publisher URL http://www.sciencedirect.com/science/article/pii/S0143400412004626?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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