title: A longitudinal analysis of angiotensin II type 1 receptor antibody and angiogenic markers in pregnancy.
abstract: BACKGROUND
  Preeclampsia can be caused by shallow trophoblast invasion and results in endothelial dysfunction. Angiotensin II type 1 receptor antibodies may have a role in both processes. Other angiogenic markers (placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin) have been shown to alter before clinically evident preeclampsia.
  
  
  OBJECTIVE
  The aim of this study is to assess the longitudinal changes and utility of biomarker angiotensin II type 1 receptor antibodies and angiogenic markers in hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia.
  
  
  METHODS
  A longitudinal prospective cohort observational study of angiogenic markers and a secondary retrospective case-control study of angiotensin II type 1 receptor antibody changes were conducted. The studies were conducted in a large tertiary metropolitan teaching hospital (Sydney, Australia). Sequential recruitment of women with a singleton pregnancy (N = 351) was undertaken. Plasma concentrations of angiotensin II type 1 receptor antibodies, placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin were measured using validated enzyme-linked immunosorbent assays at 12, 18, 28, 36, and 40 weeks' gestation and 6 weeks' postpartum. Clinical, demographic, and pregnancy data were prospectively collected. Pregnancy outcomes were classified as normotensive, gestational hypertension, or preeclampsia. Analyses were carried out using software and significance set at P < .05.
  
  
  RESULTS
  In all, 351 women were recruited, 17 developed gestational hypertension, and 18 developed preeclampsia. Women with preeclampsia at baseline were heavier (P = .015), were taller (P = .046), and had higher systolic (P = .029) and diastolic (P = .006) blood pressure. The preeclampsia group had higher soluble fms-like tyrosine kinase-1 from ≥28 weeks (P = .003) and lower placental growth factor from 18 weeks (P = .004). Soluble endoglin and angiotensin II type 1 receptor antibodies did not vary over time or between groups. Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04).
  
  
  CONCLUSIONS
  Angiogenic markers vary longitudinally during pregnancy and placental growth factor and soluble fms-like tyrosine kinase-1 have a role for predicting and diagnosing preeclampsia later in disease. Our data show that angiotensin II type 1 receptor antibodies are not sensitive for disease and hence not useful as a biomarker. Larger studies are required to describe the role and functionality of angiotensin II type 1 receptor antibodies in preeclampsia.
authors: School of Medicine, Western Sydney University, Sydney, Australia; Heart Research Institute, Sydney, Australia. Electronic address: dr.saggarwal85@gmail.com.
authors: Shikha
authors: S
authors: Aggarwal
authors: Royal Prince Alfred Hospital, Sydney, Australia.
authors: Neroli
authors: N
authors: Sunderland
authors: Department of Renal Medicine, South Western Sydney Local Health District, Sydney, Australia.
authors: Charlene
authors: C
authors: Thornton
authors: Heart Research Institute, Sydney, Australia.
authors: Bei
authors: B
authors: Xu
authors: School of Medicine, Western Sydney University, Sydney, Australia; Heart Research Institute, Sydney, Australia; Department of Renal Medicine, South Western Sydney Local Health District, Sydney, Australia.
authors: Annemarie
authors: A
authors: Hennessy
authors: School of Medicine, Western Sydney University, Sydney, Australia; Heart Research Institute, Sydney, Australia; Department of Renal Medicine, South Western Sydney Local Health District, Sydney, Australia.
authors: Angela
authors: A
authors: Makris
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D006063:Chorionic Gonadotropin / Q000097:blood; D000071063:Endoglin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000276:immunology; D008137:Longitudinal Studies; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D001323:Autoantibodies; D006063:Chorionic Gonadotropin; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D044140:Receptor, Angiotensin, Type 1; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: angiotensin II type 1 receptor antibodies; placental growth factor; preeclampsia; soluble endoglin; soluble fms-like tyrosine kinase 1