Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension

Abstract

Background: Pulmonary arterial hypertension is a disorder of vascular remodeling causing increased resistance to pulmonary blood flow. The expression of proteins in lungs from pulmonary arterial hypertension patients was investigated in an unbiased approach to further understand the pathobiology of this disease.

Methods and results: Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 8 patients with pulmonary arterial hypertension and 8 control subjects. More than 300 proteins were detected. On the basis of robust criteria, the levels of 25 proteins varied between the 2 groups. The majority of upregulated proteins were associated with cell growth, proliferation, and cell metabolism. Novel findings included an increased expression of chloride intracellular channel 4, receptor for advanced glycation end products, and periostin. Increased expression of chloride intracellular channel 4, a multifunctional protein involved in angiogenesis, and several signaling pathways implicated in pulmonary arterial hypertension--transforming growth factor-β, vascular endothelial growth factor, and bone morphogenetic protein--was confirmed by Western blotting and localized predominantly to endothelial cells in occlusive and plexiform vascular lesions.

Conclusions: Label-free proteomics identified differences in the expression of several proteins in the pulmonary arterial hypertension lung, many of which are relevant to the disease process. Increased expression of chloride intracellular channel 4 may be pertinent to the disorganized angiogenesis of plexiform lesions.