proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease

• Published in: Proteomics (Weinheim) Vol. 9; no. 11; pp. 2929 - 2945
• Main Authors: Blumenstein, Marion, McMaster, Michael T, Black, Michael A, Wu, Steven, Prakash, Roneel, Cooney, Janine, McCowan, Lesley M.E, Cooper, Garth J.S, North, Robyn A
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.06.2009; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Adult; alpha 1-Antichymotrypsin - metabolism; Analysis of Variance; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biomarkers - blood; Blood Proteins - metabolism; Cardiovascular Diseases - blood; Chromatography, Liquid; DIGE; Diseases of mother, fetus and pregnancy; Electrophoresis, Gel, Two-Dimensional; Female; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Miscellaneous; Plasma biomarkers; Pre-Eclampsia - blood; Preeclampsia; Pregnancy; Pregnancy. Fetus. Placenta; Proteins; Proteome - metabolism; Proteomics - methods; Small for gestational age; Tandem Mass Spectrometry; Genetic mapping; Intrauterine growth retardation; DIGE; Pregnancy disorders; Plasma biomarkers; Low birth weight; Biological marker; Cardiovascular disease; Identification; Pregnancy toxemia; Pregnancy; Fetal diseases; Newborn diseases; Prematurity; Preeclampsia; Genetic linkage; Proteomics; Small for gestational age
• ISSN: 1615-9853; 1615-9861
• DOI: 10.1002/pmic.200800625

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.