Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model
2013 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 183, no 5, 1425-1436 p.Article in journal (Refereed) Published
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 retinal, 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.
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA , 2013. Vol. 183, no 5, 1425-1436 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-102082DOI: 10.1016/j.ajpath.2013.07.022ISI: 000326553400010OAI: oai:DiVA.org:liu-102082DiVA: diva2:668947
Funding Agencies|NIH|P20RR018728|National Institute of Environmental Health Sciences|P42ES013660|Rhode Island Research Alliance Collaborative Research Award|2009-28|2013-12-022013-11-292014-08-26