title: Urinary excretion of C5b-9 is associated with the anti-angiogenic state in severe preeclampsia.
abstract: OBJECTIVE
  Severe preeclampsia has been independently linked to complement dysregulation and angiogenic imbalance; however, the relationship between complement and angiogenic factors in human pregnancy is unclear.
  
  
  METHODS
  Utilizing existing biomarkers, our study sought to better understand this relationship in active disease. We performed a case-control study, enrolling 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension. Levels of complement components (C3a, C5a, and C5b-9) and angiogenic markers [basic fibroblast growth factor (bFGF), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)] were measured simultaneously.
  
  
  RESULTS
  Compared to both hypertensive and non-hypertensive controls, severe preeclampsia was associated with increased plasma sFlt-1, decreased plasma VEGF and PlGF, decreased urinary PlGF, and increased urinary C5b-9. Urinary marker C5b-9 correlated strongly with the anti-angiogenic condition. In subjects with detectable urinary excretion of C5b-9, median plasma levels of sFlt-1 were significantly greater (32,029 versus 4556 pg/mL, P < 0.0001) and levels of PlGF (15.6 versus 226 pg/mL, P < 0.0001) and VEGF (119 versus 153 pg/mL, P = 0.001) were significantly lower.
  
  
  CONCLUSIONS
  More so than plasma complement markers, urinary C5b-9 may a useful measure to link complement dysregulation with angiogenic imbalance in severe preeclampsia.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Guseh
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Feinberg
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Dawood
authors.forename: Hidemi S
authors.initials: HS
authors.lastname: Yamamoto
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Richard M
authors.initials: RM
authors.lastname: Burwick
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D015938:Complement Membrane Attack Complex / Q000652:urine*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000652:urine; D005500:Follow-Up Studies; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000652:urine*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000652:urine; D042461:Vascular Endothelial Growth Factor A / Q000652:urine; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000652:urine
chemical_list: D015415:Biomarkers; D015938:Complement Membrane Attack Complex; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenic proteins; C5b-9; complement system proteins; preeclampsia