Title |
Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model
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Published in |
American Journal of Pathology, September 2013
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DOI | 10.1016/j.ajpath.2013.07.022 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 68 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 13 | 19% |
Student > Ph. D. Student | 8 | 12% |
Researcher | 8 | 12% |
Student > Master | 5 | 7% |
Other | 4 | 6% |
Other | 11 | 16% |
Unknown | 19 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 22 | 32% |
Biochemistry, Genetics and Molecular Biology | 11 | 16% |
Agricultural and Biological Sciences | 6 | 9% |
Nursing and Health Professions | 4 | 6% |
Neuroscience | 1 | 1% |
Other | 0 | 0% |
Unknown | 24 | 35% |