title: Altered pulmonary artery endothelial-smooth muscle cell interactions in experimental congenital diaphragmatic hernia.
abstract: BACKGROUND
  Pulmonary hypertension (PH) secondary to vascular remodeling contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however mechanisms responsible are unknown. We hypothesized that pulmonary artery endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC) hyperplasia in experimental CDH.
  
  
  METHODS
  PAEC and SMC were isolated from fetal sheep with experimental CDH and controls. SMC growth was assessed alone and with SOD plus catalase and during coculture with control or CDH PAEC with and without ET-1 siRNA transfection. ET-1 protein was measured in PAEC and SMC lysates and supernatant. ROS production was measured in normal and CDH PAECs with and without ET-1 siRNA. PAEC growth and tube formation were measured with SOD plus catalase.
  
  
  RESULTS
  CDH SMC growth was decreased and increased with coculture with CDH PAEC more than control PAEC. Treatment of CDH PAEC with SOD plus catalase or ET-1 siRNA prevented the increase in SMC growth seen with coculture. ET-1 protein was increased in CDH PAEC and SMC. ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA. SOD plus catalase restored CDH PAEC growth and tube formation.
  
  
  CONCLUSIONS
  PAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC.
authors.affiliation: 1] Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Acker
authors.affiliation: 1] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Seedorf
authors.affiliation: 1] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Abman
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Eva
authors.initials: E
authors.lastname: Nozik-Grayck
authors.affiliation: Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kuhn
authors.affiliation: Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Partrick
authors.affiliation: 1] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Jason
authors.initials: J
authors.lastname: Gien
mesh_terms: D000818:Animals; D000077300:Bosentan; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D019332:Endothelin-1 / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011651:Pulmonary Artery / Q000196:embryology* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D013449:Sulfonamides / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D002374:Catalase; D013482:Superoxide Dismutase; D000077300:Bosentan