• Walter Klepetko, Andrea Olschewski, Horst Olschewski, Leigh M Marsh, Bahil Ghanim, and Grazyna Kwapiszewska.
• 1 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
• Am. J. Respir. Crit. Care Med.. 2014 Jul 1;190(1):98-111.

RationaleThe development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity.ObjectivesTo elucidate whether vascular remodeling in a well-characterized PH-COPD and PH-IPF patient cohort results from similar or divergent molecular changes.MethodsVascular 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.Measurements And Main ResultsPulmonary 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.ConclusionsDespite 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.

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