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

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, ma...

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Published in:	Placenta (Eastbourne) Vol. 34; no. 2; pp. 182 - 186
Main Authors:	Mistry, H.D., Kurlak, L.O., Broughton Pipkin, F.
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 01.02.2013 Elsevier
Subjects:	Angiotensin receptors Angiotensinogen Angiotensinogen - metabolism Biological and medical sciences Case-Control Studies Embryology: invertebrates and vertebrates. Teratology Female Fundamental and applied biological sciences. Psychology Glutathione Peroxidase - metabolism Humans Immunohistochemistry Infant, Low Birth Weight Infant, Newborn Internal Medicine Male Obstetrics and Gynecology Oxidative Stress Placenta Placenta - metabolism Pre-eclampsia Pre-Eclampsia - metabolism Pregnancy Pregnancy. Parturition. Lactation Pro-renin receptor Receptor, Angiotensin, Type 1 - metabolism Receptor, Angiotensin, Type 2 - metabolism Receptors, Cell Surface - metabolism Renin-Angiotensin System - physiology Renin–angiotensin system Trophoblasts - metabolism Vertebrates: reproduction Renin–angiotensin system Angiotensinogen Pro-renin receptor Placenta Pre-eclampsia Angiotensin receptors Oxidative stress Vertebrata Renin angiotensin system Mammalia Pregnancy disorders Fetal membrane Preeclampsia Pregnancy toxemia
ISSN:	0143-4004, 1532-3102, 1532-3102
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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. 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). 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. 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.
AbstractList	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. 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). 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. 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. 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.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.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).HYPOTHESISPre-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).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.RESULTSAT1R 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.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.CONCLUSIONSThe 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. 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. 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). 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. 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. AbstractThere 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 measuresHypothesis: 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). ResultsAT1R 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. ConclusionsThe 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.
Author	Broughton Pipkin, F. Mistry, H.D. Kurlak, L.O.
Author_xml	– sequence: 1 givenname: H.D. surname: Mistry fullname: Mistry, H.D. email: hiten.mistry@kcl.ac.uk organization: Division of Women's Health, King's College London, Women's Health Academic Centre, KHP, 10th Floor, North Wing, St. Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK – sequence: 2 givenname: L.O. surname: Kurlak fullname: Kurlak, L.O. organization: Division of Obstetrics & Gynaecology, School of Clinical Sciences, University of Nottingham, City Hospital, Nottingham, UK – sequence: 3 givenname: F. surname: Broughton Pipkin fullname: Broughton Pipkin, F. organization: Division of Obstetrics & Gynaecology, School of Clinical Sciences, University of Nottingham, City Hospital, Nottingham, UK
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Keywords	Renin–angiotensin system Angiotensinogen Pro-renin receptor Placenta Pre-eclampsia Angiotensin receptors Oxidative stress Vertebrata Renin angiotensin system Mammalia Pregnancy disorders Fetal membrane Preeclampsia Pregnancy toxemia
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Snippet	There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin... AbstractThere is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased...
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SubjectTerms	Angiotensin receptors Angiotensinogen Angiotensinogen - metabolism Biological and medical sciences Case-Control Studies Embryology: invertebrates and vertebrates. Teratology Female Fundamental and applied biological sciences. Psychology Glutathione Peroxidase - metabolism Humans Immunohistochemistry Infant, Low Birth Weight Infant, Newborn Internal Medicine Male Obstetrics and Gynecology Oxidative Stress Placenta Placenta - metabolism Pre-eclampsia Pre-Eclampsia - metabolism Pregnancy Pregnancy. Parturition. Lactation Pro-renin receptor Receptor, Angiotensin, Type 1 - metabolism Receptor, Angiotensin, Type 2 - metabolism Receptors, Cell Surface - metabolism Renin-Angiotensin System - physiology Renin–angiotensin system Trophoblasts - metabolism Vertebrates: reproduction
Title	The placental renin–angiotensin system and oxidative stress in pre-eclampsia
URI	https://www.clinicalkey.com/#!/content/1-s2.0-S0143400412004626 https://www.clinicalkey.es/playcontent/1-s2.0-S0143400412004626 https://dx.doi.org/10.1016/j.placenta.2012.11.027 https://www.ncbi.nlm.nih.gov/pubmed/23246097 https://www.proquest.com/docview/1284290643
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