title: Gestational hypertension, preeclampsia and intrauterine growth restriction induce dysregulation of cardiovascular and cerebrovascular disease associated microRNAs in maternal whole peripheral blood.
abstract: OBJECTIVE
  To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out.
  
  
  RESULTS
  The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications.
  
  
  CONCLUSIONS
  Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood.
authors.affiliation: Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: ilona.hromadnikova@lf3.cuni.cz.
authors.forename: Ilona
authors.initials: I
authors.lastname: Hromadnikova
authors.affiliation: Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: kotlabova.k@seznam.cz.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kotlabova
authors.affiliation: Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: Lucie.Hympanova@seznam.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Hympanova
authors.affiliation: Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: ladislav.krofta@upmd.cz.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Krofta
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000097:blood / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000235:genetics*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics*; D011247:Pregnancy
chemical_list: D035683:MicroRNAs
keywords: Cardio/cerebrovascular diseases; Gestational hypertension; Intrauterine growth restriction; MicroRNA; Preeclampsia