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Hoffmann, J; Wilhelm, J; Marsh, LM; Ghanim, B; Klepetko, W; Kovacs, G; Olschewski, H; Olschewski, A; Kwapiszewska, G.
Distinct differences in gene expression patterns in pulmonary arteries of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis with pulmonary hypertension.
Am J Respir Crit Care Med. 2014; 190(1):98-111 Doi: 10.1164/rccm.201401-0037OC
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Leading authors Med Uni Graz: Hoffmann Julia; Kwapiszewska-Marsh Grazyna
Co-authors Med Uni Graz: Kovacs Gabor; Marsh Leigh; Olschewski Andrea; Olschewski Horst
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Abstract:: The development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity. To elucidate whether vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort results from similar or divergent molecular changes. 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. 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. 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.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Airway Remodeling - genetics; Airway Remodeling - physiology; Airway Remodeling -; Female -; Genome-Wide Association Study -; Humans -; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - pathology; Idiopathic Pulmonary Fibrosis - complications; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - pathology; Laser Capture Microdissection -; Male -; Middle Aged -; Prognosis -; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - pathology; Real-Time Polymerase Chain Reaction -; Transcriptome -
Find related publications in this database (Keywords): pulmonary hypertension; microarrays; laser capture microdissection; remodeling