title: Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia.
abstract: BACKGROUND
  Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterized by the herniation of abdominal organs into the chest cavity. The high mortality and morbidity of CDH patients are primarily caused by the associated pulmonary hypertension (PH), characterized by the thickening of the vascular media and adventitia. The media consist of heterogeneous populations of vascular smooth muscle cells (VSMC), ranging from synthetic to the characteristic contractile cells. VSMCs are influenced by developmental and environmental cues and may play a role in the development of the structural changes observed in CDH patients. Therefore, we hypothesized that the distribution of the VSMC populations may already be different at the origin of CDH development.
  
  
  METHODS
  We analyzed the protein expression of specific markers associated with synthetic and contractile VSMC phenotypes in human lungs at different developmental stages. Next, we compared lungs of premature and term CDH patients, as well as patients with lung hypoplasia due to renal agenesis or PROM, with age-matched controls.
  
  
  RESULTS
  Synthetic and contractile VSMCs are distributed in a temporal and spatial specific pattern along the proximodistal axis of the lung. CDH patients have more abundant contractile VSMCs which are also more distally distributed. This different distribution pattern is already observed from 19 weeks of gestation onwards.
  
  
  CONCLUSIONS
  Our data suggest that the more extensive distribution of contractile VSMCs is associated with an early maturation of the pulmonary vasculature, contrasting the concept that CDH might be the result of delayed maturation of the epithelium.
authors.affiliation: Department of Pediatric Surgery, Erasmus MC Rotterdam, The Netherlands. i.sluiter@erasmusmc.nl
authors.forename: Ilona
authors.initials: I
authors.lastname: Sluiter
authors.forename: Irene
authors.initials: I
authors.lastname: van der Horst
authors.forename: Paul
authors.initials: P
authors.lastname: van der Voorn
authors.forename: Anne
authors.initials: A
authors.lastname: Boerema-de Munck
authors.forename: Marjon
authors.initials: M
authors.lastname: Buscop-van Kempen
authors.forename: Ronald
authors.initials: R
authors.lastname: de Krijger
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Irwin
authors.initials: I
authors.lastname: Reiss
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Rottier
mesh_terms: D002454:Cell Differentiation; D006548:Hernia, Diaphragmatic / Q000150:complications / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities / Q000166:cytology / Q000196:embryology; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011651:Pulmonary Artery / Q000166:cytology; D011667:Pulmonary Veins / Q000166:cytology; D054840:Retinol-Binding Proteins, Cellular / Q000032:analysis / Q000096:biosynthesis; D024745:Smooth Muscle Myosins / Q000032:analysis / Q000096:biosynthesis
chemical_list: D054840:Retinol-Binding Proteins, Cellular; D024745:Smooth Muscle Myosins