title: Distinct differences in gene expression patterns in pulmonary arteries of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis with pulmonary hypertension.
abstract: BACKGROUND
  The development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity.
  
  
  OBJECTIVE
  To elucidate whether vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort results from similar or divergent molecular changes.
  
  
  METHODS
  Vascular remodeling of donor, PH-COPD, and PH-IPF pulmonary arteries was assessed. Laser capture microdissected pulmonary artery profiles in combination with whole genome microarrays were performed.
  
  
  RESULTS
  Pulmonary arteries from patients with COPD and IPF with PH exhibited remodeling of vascular layers and reduction of lumen area. Pathway analyses comparing normalized gene expression profiles obtained from patients with PH-IPF or PH-COPD revealed the retinol and extracellular matrix (ECM) receptor interaction to be the most perturbed processes. Within the ECM-receptor pathway, differential regulation of 5 out of the top 10 results (collagen, type III, α-1; tenascin C; collagen, type VI, α-3; thrombospondin 2; and von Willebrand factor) were verified by real-time polymerase chain reaction and immunohistochemical staining.
  
  
  CONCLUSIONS
  Despite clinical and histologic vascular remodeling in all patients with PH-COPD and PH-IPF, differential gene expression pattern was present in pulmonary artery profiles. Several genes involved in retinol metabolism and ECM receptor interaction enable discrimination of vascular remodeling in PH-IPF or PH-COPD. This suggests that pulmonary arterial remodeling in PH-COPD and PH-IPF is caused by different molecular mechanisms and may require specific therapeutic options.
authors.affiliation: 1 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Leigh M
authors.initials: LM
authors.lastname: Marsh
authors.forename: Bahil
authors.initials: B
authors.lastname: Ghanim
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Gabor
authors.initials: G
authors.lastname: Kovacs
authors.forename: Horst
authors.initials: H
authors.lastname: Olschewski
authors.forename: Andrea
authors.initials: A
authors.lastname: Olschewski
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kwapiszewska
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000235:genetics / Q000502:physiology; D001317:Austria; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011651:Pulmonary Artery / Q000473:pathology* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
keywords: laser capture microdissection; microarrays; pulmonary hypertension; remodeling