title: Angiotensin II type 1 receptor autoantibody (AT1-AA)-mediated pregnancy hypertension.
abstract: Autoantibodies can cause complications in pregnancy. Preeclampsia is the leading cause of maternal and fetal morbidity and mortality during pregnancy. Overall, 5-10% of all pregnancies worldwide develop preeclampsia. Women who developed preeclampsia and their children have an increased risk to suffer from cardiovascular diseases later in life. In preeclampsia, agonistic autoantibodies against the angiotensin II type 1 receptor autoantibodies (AT1-AA) are described. They induce NADPH oxidase and the MAPK/ERK pathway leading to NF-κB and tissue factor activation. AT1-AA are detectable in animal models of preeclampsia and are responsible for elevation of soluble fms-related tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), oxidative stress, and endothelin-1, all of which are enhanced in preeclamptic women. AT1-AA can be detected in pregnancies with abnormal uterine perfusion and increased resistance index as well as in patients with systemic sclerosis and renal allograft rejection. This review discusses the current knowledge about the AT1-AA, its signaling, and their impact in pregnancy complications and other autoimmune disorders.
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D000071063:Endoglin; D019332:Endothelin-1 / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000276:immunology*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; C064206:ENG protein, human; D000071063:Endoglin; D019332:Endothelin-1; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D013925:Thromboplastin; D019255:NADPH Oxidases; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1