Proteomic Analyses of Endarterectomized Tissues from Patients with Chronic Thromboembolic Pulmonary Hypertension

Abstract

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Proteomics offers an approach to overview the molecular activities and signal transduction pathways involved in specific disease processes. Objectives: In this study, the expression of proteins in endarterectomized tissues from patients with CTEPH was investigated in a novel strategy to explore the pathophysiology of this disease. Methods: We used the iTRAQ (isobaric tag for relative and absolute quantitation) approach combined with a Thermo Scientific Q Exactive MS analysis to compare the protein profiles in endarterectomized tissues from CTEPH patients and that of the control samples (mixture of cultured human pulmonary artery endothelial cells, human pulmonary artery smooth muscle cells, and human pulmonary fibroblasts). GO and KEGG analyses were performed to understand the functional classification and molecular activities of all the tissue-specific proteins, and the involved signal transduction pathways. Results: Six hundred and seventy-nine tissue-specific proteins were detected. Bioinformatic analysis showed that the major biological processes involving these proteins were: response to wounding, defense response, acute inflammatory response, immune response, complement activation, and blood coagulation. The main pathways involved were: complement and coagulation cascade, systemic lupus erythematosus, extracellular matrix-receptor interaction, cell adhesion molecules, FcεRI signaling, and leukocyte transendothelial migration. Conclusions: The present study revealed that immune and defense response might play an important role in CTEPH.