title: The placental renin-angiotensin system and oxidative stress in pre-eclampsia.
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.
  
  
  OBJECTIVE
  
  
  
  OBJECTIVE
  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.
authors.affiliation: 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. hiten.mistry@kcl.ac.uk
authors.forename: H D
authors.initials: HD
authors.lastname: Mistry
authors.forename: L O
authors.initials: LO
authors.lastname: Kurlak
authors.forename: F
authors.initials: F
authors.lastname: Broughton Pipkin
mesh_terms: D000808:Angiotensinogen / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011956:Receptors, Cell Surface; D000808:Angiotensinogen; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D000093342:Prorenin Receptor