title: Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition.
abstract: Patent ductus arteriosus (PDA) in the newborn is the most common congenital heart anomaly and is significantly more common in preterm infants. Contemporary pharmacological treatment is effective in only 70-80% of the cases. Moreover, indomethacin or ibuprofen, which are used to close a PDA may be accompanied by serious side effects in premature infants. To explore the novel molecular pathways, which may be involved in the maturation and closure of the ductus arteriosus (DA), we used fetal and neonatal sheep to test the hypothesis that maturational development of DA is associated with significant alterations in specific mRNA expression.
  
  
  
  We conducted oligonucleotide microarray experiments on the isolated mRNA from DA and ascending aorta from three study groups (premature fetus-97 ± 0 d, near-term fetus-136 ± 0.8 d, and newborn lamb-12 ± 0 h). We compared the alterations in mRNA expression in DA and aorta to identify genes specifically involved in DA maturation.
  
  
  
  Results demonstrate significant changes in wingless-integrin1, thrombospondin 1, receptor activator of nuclear factor-kappa B, nitric oxide synthase, and retinoic acid receptor activation signaling pathways.
  
  
  
  We conclude that these pathways may play an important role during both development and postnatal DA closure and warrant further investigation.
authors.affiliation: Center for Perinatal Biology, Division of Basic Sciences, Loma Linda University, Loma Linda, California.
authors.forename: Ravi
authors.initials: R
authors.lastname: Goyal
authors.affiliation: Center for Perinatal Biology, Division of Basic Sciences, Loma Linda University, Loma Linda, California.
authors.forename: Dipali
authors.initials: D
authors.lastname: Goyal
authors.affiliation: Center for Perinatal Biology, Division of Basic Sciences, Loma Linda University, Loma Linda, California.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.affiliation: Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, California.
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D004373:Ductus Arteriosus / Q000503:physiopathology*; D004374:Ductus Arteriosus, Patent / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011270:Pregnancy, Animal; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012756:Sheep; D019700:Thrombospondin 1 / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D053246:Receptor Activator of Nuclear Factor-kappa B; D018168:Receptors, Retinoic Acid; D019700:Thrombospondin 1; D051155:Wnt1 Protein; D019001:Nitric Oxide Synthase