RT Journal Article
SR Electronic
T1 Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1324
OP 1330
DO 10.1183/09031936.0084112
VO 41
IS 6
A1 Nina M. Patel
A1 Steven M. Kawut
A1 Sanja Jelic
A1 Selim M. Arcasoy
A1 David J. Lederer
A1 Alain C. Borczuk
YR 2013
UL http://erj.ersjournals.com/content/41/6/1324.abstract
AB 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.