Transthyretin is dysregulated in preeclampsia, and its native form prevents the onset of disease in a preclinical mouse model

Satyan S. Kalkunte, Stefan Neubeck, Wendy E. Norris, Shi Bin Cheng, Stefan Kostadinov, Dang Vu Hoang, Aftab Ahmed, Ferdinand Von Eggeling, Zahir Shaikh, James Padbury, Goran Berg, Anders Olofsson, Udo R. Markert, Surendra Sharma

Research output: Contribution to journalArticlepeer-review

Abstract

Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.

Original languageEnglish (US)
Pages (from-to)1425-1436
Number of pages12
JournalAmerican Journal of Pathology
Volume183
Issue number5
DOIs
StatePublished - Nov 2013
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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