title: Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated whether Egr-1 is also associated with neointimal-type vascular remodeling in different forms of human PAH or pulmonary hypertension.
  
  
  METHODS
  Using immunohistochemistry, we studied Egr-1 expression specifically in a wide morphologic spectrum of pulmonary arteries in the lung tissue of 72 patients with different forms and stages of PAH, specifically idiopathic PAH (n = 18), advanced-stage congenital heart disease‒associated PAH (PAH-CHD) (n = 21), early-stage PAH-CHD (n = 19) and non-neointimal hypoxic pulmonary hypertension (PH) (n = 4), and controls (n = 10).
  
  
  RESULTS
  In PAH patients, pulmonary vascular expression of Egr-1 protein was abundant, whereas it was sporadic in non-neointimal (hypoxic) PH patients and controls. In PAH-CHD, protein expression was more pronounced in patients with advanced vascular lesions compared to those with less advanced lesions, such as medial hypertrophy.
  
  
  CONCLUSIONS
  Pulmonary vascular Egr-1 expression is significantly increased in patients with PAH, appears specifically associated with neointimal-type vascular remodeling, and correlates with disease progression. These data translate the critical role of Egr-1 in the development of experimental PAH to human pulmonary vascular disease forms.
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: d.e.van.der.feen01@umcg.nl.
authors.forename: Diederik E
authors.initials: DE
authors.lastname: van der Feen
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dickinson
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Bartelds
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marinus A J
authors.initials: MA
authors.lastname: Borgdorff
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology, Martini Hospital Groningen, Groningen, The Netherlands.
authors.forename: Hannie
authors.initials: H
authors.lastname: Sietsma
authors.affiliation: Service de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, Faculté de Médecine Paris V, Paris, France.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Lévy
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
mesh_terms: D000328:Adult; D001706:Biopsy; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D065627:Familial Primary Pulmonary Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D004247:DNA
keywords: congenital heart disease; early growth response-1; immunohistochemistry; lung biopsies; neointimal remodeling; pulmonary arterial hypertension