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

Cissy C. Zhou, Shakil Ahmad, Tiejuan Mi, Shahrzad Abbasi, Lingwei Xia, Mary-Clare Day, Susan M. Ramin, Asif Ahmed, Rodney E. Kellems, Yang Xia

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages1010-1019
Number of pages10
JournalHypertension
Volume51
Issue number4
DOIs
Publication statusPublished - 2 Jul 2008

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NFATC Transcription Factors
Vascular Endothelial Growth Factor Receptor-1
Angiotensin Type 1 Receptor
Calcineurin
Pre-Eclampsia
Autoantibodies
Mothers
Fetal Mortality
Angiotensin Receptors
Trophoblasts
Tacrolimus
Small Interfering RNA
Cell Movement
Catalytic Domain
Endothelial Cells
Immunoglobulin G
Morbidity
Pregnancy
Messenger RNA

Bibliographical note

© 2008, Wolters Kluwer Health

Keywords

  • preeclampsia
  • renin-angiotensin system
  • angiotensin receptor
  • autoantibody
  • angiogenesis
  • cell signaling

Cite this

Zhou, Cissy C. ; Ahmad, Shakil ; Mi, Tiejuan ; Abbasi, Shahrzad ; Xia, Lingwei ; Day, Mary-Clare ; Ramin, Susan M. ; Ahmed, Asif ; Kellems, Rodney E. ; Xia, Yang. / 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. In: Hypertension. 2008 ; Vol. 51, No. 4. pp. 1010-1019.
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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.; Xia, Yang.

In: Hypertension, Vol. 51, No. 4, 02.07.2008, p. 1010-1019.

Research output: Contribution to journalArticle

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AU - Ahmad, Shakil

AU - Mi, Tiejuan

AU - Abbasi, Shahrzad

AU - Xia, Lingwei

AU - Day, Mary-Clare

AU - Ramin, Susan M.

AU - Ahmed, Asif

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AU - Xia, Yang

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