Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 183, Issue 5, Pages 1425-1436Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.07.022
Keywords
-
Categories
Funding
- NIH [P20RR018728]
- National Institute of Environmental Health Sciences [P42ES013660]
- Rhode Island Research Alliance Collaborative Research Award [2009-28]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available