title: The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia.
abstract: BACKGROUND
  Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation. To dissect the contribution of systemic inflammation and anti-angiogenic factors in preeclampsia, we investigated the relationships between the circulating markers of neutrophil activation and anti-angiogenic factors in severe preeclampsia or systemic inflammatory state during pregnancy.
  
  
  RESULTS
  Serum sEng, sFlt-1, placenta growth factor, interleukin-6 (IL-6), calprotectin, and plasma α-defensins concentrations were measured by ELISA in 88 women of similar gestational age stratified as: severe preeclampsia (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL, n = 27). Neutrophil activation occurred in sPE and SIR, as α-defensins and calprotectin concentrations were two-fold higher in both groups compared to CRL (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P < 0.001) were ≈20-fold higher in sPE compared to CRL, but were not elevated in SIR. In women with sPE, anti-angiogenic factors were not correlated with markers of neutrophil activation (α-defensins, calprotectin) or inflammation (IL-6).
  
  
  CONCLUSIONS
  Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia.
authors.affiliation: University/BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. wendaramma4585@gmail.com
authors.forename: Wenda
authors.initials: W
authors.lastname: Ramma
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Antonette T
authors.initials: AT
authors.lastname: Dulay
authors.forename: Unzila Ali
authors.initials: UA
authors.lastname: Nayeri
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018375:Neutrophil Activation; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy
chemical_list: D043925:Angiogenesis Inducing Agents