A proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease |
| |
Authors: | Marion Blumenstein Michael T. McMaster Michael A. Black Steven Wu Roneel Prakash Janine Cooney Lesley M. E. McCowan Garth J. S. Cooper Robyn A. North |
| |
Affiliation: | 1. School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand;2. Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA;3. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA;4. Bioinformed Ltd, Dunedin, New Zealand;5. Bioinformatics Institute, Faculty of Science, University of Auckland, Auckland, New Zealand;6. HortResearch, Hamilton, New Zealand;7. Department of Obstetrics & Gynecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;8. Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, UK |
| |
Abstract: | Preeclampsia (PE) is a common, potentially life‐threatening pregnancy syndrome triggered by placental factors released into the maternal circulation, resulting in maternal vascular dysfunction along with activated inflammation and coagulation. Currently there is no screening test for PE. We sought to identify differentially expressed plasma proteins in women who subsequently develop PE that may perform as predictive biomarkers. In seven DIGE experiments, we compared the plasma proteome at 20 wk gestation in women who later developed PE with an appropriate birth weight for gestational age baby (n=27) or a small for gestational age baby (n=12) to healthy controls with uncomplicated pregnancies (n=57). Of the 49 differentially expressed spots associated with PE‐appropriate for gestational age, PE‐small for gestational age or both (p<0.05, false discovery rate corrected), 39 were identified by LC‐MS/MS. Two protein clusters that accurately (>90%) classified women at risk of developing PE were identified. Immunoblots confirmed the overexpression of fibrinogen γ chain and α‐1‐antichymotrypsin in plasma prior to PE. The proteins identified are involved in lipid metabolism, coagulation, complement regulation, extracellular matrix remodeling, protease inhibitor activity and acute‐phase responses, indicating novel synergism between pathways involved in the pathogenesis of PE. Our findings are remarkably similar to recently identified proteins complexed to high‐density lipoprotein and linked to cardiovascular disease. |
| |
Keywords: | DIGE Plasma biomarkers Preeclampsia Pregnancy Small for gestational age |
|
|