title: Autoantibody against angiotensin AT1 receptor from preeclamptic patients enhances collagen-induced human platelet aggregation.
abstract: Hypercoagulability, platelet activation, and thrombocytopenia are the chief characteristics of preeclampsia, but their responsible underlying molecular mechanisms remain obscure. Recent studies have demonstrated that the autoantibody against angiotensin II type 1 receptor (AT1-AA) constitutes a novel risk factor for preeclampsia. However, the role of AT1-AA in platelet activation and hypercoagulability in preeclampsia has never been investigated. In the present study, we determined whether AT1-AA promotes platelet aggregation in vitro, and dissected the potential underlying mechanisms. AT1-AA was detected by enzyme-linked immunosorbent assay. After immunoglobulin G fractions purified from the preeclamptic patient positive sera were added to platelets isolated from healthy volunteers, platelet aggregation and intracellular Ca(2+) levels were detected. AT1-AA significantly enhanced in vitro collagen-induced platelet aggregation, an effect blocked by the AT1 receptor antagonist losartan. Additionally, AT1-AA increased and maintained collagen-induced cytosolic calcium concentration throughout the experiment. We demonstrated for the first time that AT1-AA significantly promotes collagen-induced platelet aggregation through angiotensin type 1 receptor activation in vitro, potentially via increased intracellular Ca(2+) concentration, supporting AT1-AA as a potential contributor to the hypercoagulable state of preeclampsia.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Kehua
authors.initials: K
authors.lastname: Bai
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Suli
authors.initials: S
authors.lastname: Zhang
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000276:immunology; D003094:Collagen / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D003094:Collagen; D002118:Calcium
keywords: angiotensin II type 1 receptor; autoantibody; calcium; platelet aggregation