Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling

Zhou, Cissy C., Ahmad, Shakil, Mi, Tiejuan, Abbasi, Shahrzad, Xia, Lingwei, Day, Mary-Clare, Ramin, Susan M., Ahmed, Asif, Kellems, Rodney E. and Xia, Yang (2008). Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling. Hypertension, 51 (4), pp. 1010-1019.

Abstract

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention.

Publication DOI: https://doi.org/10.1161/HYPERTENSIONAHA.107.097790
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences > Cellular and Molecular Biomedicine
Aston Medical School
Life & Health Sciences
Additional Information: © 2008, Wolters Kluwer Health
Uncontrolled Keywords: preeclampsia,renin-angiotensin system,angiotensin receptor,autoantibody,angiogenesis,cell signaling,Internal Medicine
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://hyper.ah ... ntent/51/4/1010 (Publisher URL)
Published Date: 2008-07-02
Authors: Zhou, Cissy C.
Ahmad, Shakil ( 0000-0002-9294-0475)
Mi, Tiejuan
Abbasi, Shahrzad
Xia, Lingwei
Day, Mary-Clare
Ramin, Susan M.
Ahmed, Asif
Kellems, Rodney E.
Xia, Yang

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