Introduction and Objective Pulmonary arterial hypertension (PAH) is a poorly understood debilitating disorder which is characterised by increased resistance to the pulmonary blood flow caused by the remodelling of the pulmonary arteries. The objective of this study was to identify differentially expressed proteins in lungs of patients with PAH that may further help us understand the pathobiology of this disease.

Methods Label-free liquid chromatography tandem mass spectrometry was used to generate protein expression profiles from the lung homogenates of 8 PAH patients and 8 Controls. Progenesis-MS software was then used to compare the relative levels of detected proteins.

Results After application of stringent criteria to confirm proteins identities and to detect differences, 27 proteins were found to be differentially expressed from a total of 363 proteins. Proteins that had increased expression in PAH lungs were mainly involved in cell growth, proliferation and cell metabolism. Examples of affected proteins included chloride intracellular channel 4 (CLIC4) and periostin which were both up-regulated and these findings were confirmed by immunoblotting. CLIC4 is known to play a vital role in angiogenesis and has also been implicated in transforming growth factor-β, vascular endothelial growth factor and bone morphogenetic protein receptor two signalling pathways. Periostin is an extracellular matrix protein considered to be involved in vascular injury responses and regulation of smooth muscle cell proliferation. Immunohistochemistry studies showed predominant localisation of CLIC4 in the endothelium of remodelled pulmonary arteries and in plexiform lesions while periostin was prominent in the airways and in the neointimal layer of the remodelled pulmonary arteries.

Conclusions Many proteins that may be involved in the pathogenesis of PAH have been discovered using label free proteomics. Examples include CLIC4 and periostin, which may be involved in the remodelling of vessels in PAH.