title: Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis.
abstract: A third of patients with idiopathic pulmonary fibrosis (IPF) develop pulmonary hypertension (PH-IPF), which is associated with increased mortality. Whether an altered gene expression profile in the pulmonary vasculature precedes the clinical onset of PH-IPF is unknown. We compared gene expression in the pulmonary vasculature of IPF patients with and without PH with controls. Pulmonary arterioles were isolated using laser capture microdissection from 16 IPF patients: eight with PH (PH-IPF) and eight with no PH (NPH-IPF), and seven controls. Probe was prepared from extracted RNA, and hybridised to Affymetrix Hu133 2.0 Plus genechips. Biometric Research Branch array tools and Ingenuity Pathway Analysis software were used for analysis of the microarray data. Univariate analysis revealed 255 genes that distinguished IPF arterioles from controls (p<0.001). Mediators of vascular smooth muscle and endothelial cell proliferation, Wnt signalling and apoptosis were differentially expressed in IPF arterioles. Unsupervised and supervised clustering analyses revealed similar gene expression in PH-IPF and NPH-IPF arterioles. The pulmonary arteriolar gene expression profile is similar in IPF patients with and without coexistent PH. Pathways involved in vascular proliferation and aberrant apoptosis, which may contribute to pulmonary vascular remodelling, are activated in IPF patients.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, NY 10032, USA. np2199@columbia.edu
authors.forename: Nina M
authors.initials: NM
authors.lastname: Patel
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.forename: Sanja
authors.initials: S
authors.lastname: Jelic
authors.forename: Selim M
authors.initials: SM
authors.lastname: Arcasoy
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
mesh_terms: D000328:Adult; D000368:Aged; D001160:Arterioles / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome
keywords: DNA microarray; laser capture microdissection; pulmonary arterial hypertension; usual interstitial pneumonia