Author: ["Cissy C Zhou","Yujin Zhang","Roxanna A Irani","Hong Zhang","Tiejuan Mi","Edwina J Popek","M John Hicks","Susan M Ramin","Rodney E Kellems","Yang Xia"]
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Abstract
Direct proof that women with pre-eclampsia develop autoantibodies to the AT1 receptor, which explains the hypertension and other symptoms of the disease, is now provided. Additionally, blocking these autoantibodies or treating with losartin, a drug that targets the AT1 receptor, in a new mouse model of this condition helps ameliorate disease outcome ( pages 810–812 ). Pre-eclampsia affects approximately 5% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity in the United States and the world1,2. The clinical hallmarks of this maternal disorder include hypertension, proteinuria, endothelial dysfunction and placental defects. Advanced-stage clinical symptoms include cerebral hemorrhage, renal failure and the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. An effective treatment of pre-eclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease. Numerous recent studies3,4,5 have shown that women with pre-eclampsia possess autoantibodies, termed AT1-AAs, that bind and activate the angiotensin II receptor type 1a (AT1 receptor). We show here that key features of pre-eclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of pre-eclampsia), placental abnormalities and small fetus size appeared in pregnant mice after injection with either total IgG or affinity-purified AT1-AAs from women with pre-eclampsia. These features were prevented by co-injection with losartan, an AT1 receptor antagonist, or by an antibody neutralizing seven–amino-acid epitope peptide. Thus, our studies indicate that pre-eclampsia may be a pregnancy-induced autoimmune disease in which key features of the disease result from autoantibody-induced angiotensin receptor activation. This hypothesis has obvious implications regarding pre-eclampsia screening, diagnosis and therapy.Cite this article
Zhou, C., Zhang, Y., Irani, R. et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 14, 855–862 (2008). https://doi.org/10.1038/nm.1856 