title: Angiotensin II type 1 receptor autoantibody as a novel regulator of aldosterone independent of preeclampsia.
abstract: BACKGROUND
  Preeclamptic women and their infants have significant morbidity and mortality worldwide. Abnormal aldosterone signaling is involved in the pathogenesis of preeclampsia, and the presence of agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) during disease has been observed. The role of AT1-AA in aldosterone generation with or without disease and the long-term impact of AT1-AA circulation in blood remain unclear.
  
  
  METHODS
  We therefore assessed circulating AT1-AA and aldosterone levels in 76 patients with preeclampsia (35 severe and 41 mild), 26 patients with gestational hypertension, and 50 normotensive healthy pregnant women.
  
  
  RESULTS
  First, the correlation of AT1-AA levels was confirmed for preeclamptic patients. We report here that all AT1-AA-positive hypertensive pregnant women exhibited decreased aldosterone levels, and early-onset preeclampsia patients with high proteinuria showed an inverse correlation of aldosterone levels with AT1-AA. To study this effect in more detail, we confirmed that AT1-AA decreased aldosterone levels in pregnant rats and then demonstrated that aldosterone levels decreased in response to the chronic administration of AT1-AA into nonpregnant rats.
  
  
  CONCLUSIONS
  These results suggested that AT1-AA regulates levels of aldosterone, which was tested with cell culture studies, revealing that activation of AT1 receptors by AT1-AA directly led to abnormal aldosterone generation in a time and dose-dependent manner. We present here a mechanism for regulation of aldosterone production: AT1-AA activates AT1 receptors on adrenocortical cells independent of pregnancy, in a time and dose-dependent manner.
authors.affiliation: aDepartment of Physiology & Pathophysiology, School of Basic Medical Sciences bSchool of Heath Management and Education, Capital Medical University, Beijing cDepartment of Gynaecology & Obstetrics, The Third People's Hospital of Chengdu, Chengdu, China dDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA eBeijing Key Laboratory of Metabolic Disorders and Related Cardiovascular Diseases fDepartment of Cardiology, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Shang
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Su-Li
authors.initials: SL
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Liu
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology*; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D000450:Aldosterone