title: HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population.
abstract: BACKGROUND
  Pre-eclampsia (PE) is a hypertensive multisystem disorder, causing significant fetal-maternal mortality and morbidity worldwide. This study aims to define possible longitudinal predictive mRNA markers involved in the main pathogenic pathways of PE: inflammation [macrophage migration inhibitory factor (MIF)], hypoxia and oxidative stress [hypoxia inducible factor 1-α subunit (HIF1A) and β-site APP-cleaving enzyme-2 (BACE2)] and endothelial dysfunction [endoglin (ENG), fms-related tyrosine kinase-1 (FLT1) and vascular endothelial growth factor (VEGF)].
  
  
  METHODS
  Peripheral blood was collected from 33 singleton pregnancies characterized by a high cardiovascular profile risk sampled consecutively at 6-16; 17-23; 24-30; 31-34; ≥35 weeks followed by the Obstetrics and Gynecology Unit of the San Raffaele Hospital in Milan. A real-time quantitative PCR reaction was performed on plasma RNA.
  
  
  RESULTS
  Of the 33 women enrolled, nine developed PE. Until 23 weeks HIF1A was significantly higher in women who later developed PE compared to women who did not (p=0.049 and p=0.012 in the first and second blood collection). In the third time interval MIF (p=0.0005), FLT1 (p=0.024), ENG (p=0.0034) and BACE2 (p=0.044) appeared to be significantly increased while HIF1A was elevated even from 24 week onwards but not reaching the statistical significance. In the fourth time interval ENG mRNA still remained increased (p=0.037).
  
  
  CONCLUSIONS
  HIF1A, marker of hypoxia and oxidative stress, and MIF, marker of inflammation, seemed to be the most promising RNA markers, suggesting that hypoxia, principally, and inflammation may play an important role in PE pathogenesis.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galbiati
authors.forename: Annalisa
authors.initials: A
authors.lastname: Inversetti
authors.forename: Vincenza
authors.initials: V
authors.lastname: Causarano
authors.forename: Stefania
authors.initials: S
authors.lastname: Stenirri
authors.forename: Nadia
authors.initials: N
authors.lastname: Soriani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ambrosi
authors.forename: Luca
authors.initials: L
authors.lastname: Valsecchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Candiani
authors.forename: Laura
authors.initials: L
authors.lastname: Cremonesi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Maddalena
authors.initials: M
authors.lastname: Smid
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008137:Longitudinal Studies; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012306:Risk
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human