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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2018

Open Access 01-12-2018 | Research article

NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD

Authors: Xiaotong Guo, Yuchun Fan, Jieda Cui, Binwei Hao, Li Zhu, Xiao Sun, Jinxi He, Jiali Yang, Jianda Dong, Yanyang Wang, Xiaoming Liu, Juan Chen

Published in: BMC Pulmonary Medicine | Issue 1/2018

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Abstract

Background

Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is suggested as the consequence of emphysematous destruction of vascular bed and hypoxia of pulmonary microenvironment, mechanisms underpinning its pathogenesis however remain elusive. The dysregulated expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases and superoxide generation by pulmonary vasculatures have significant implications in the hypoxia-induced PH.

Methods

In this study, the involvement of NADPH oxidase subunit 4 (NOX4) in pulmonary arteriolar remodeling of PH in COPD was investigated by ascertaining the morphological alteration of pulmonary arteries and pulmonary blood flow using cardiac magnetic resonance imaging (cMRI), and the expression and correlation of NOX4 with pulmonary vascular remodeling and pulmonary functions in COPD lungs.

Results

Results demonstrated that an augmented expression of NOX4 was correlated with the increased volume of pulmonary vascular wall in COPD lung. While the volume of distal pulmonary arteries was inversely correlated with pulmonary functions, despite it was positively associated with the main pulmonary artery distensibility, right ventricular myocardial mass end-systolic and right ventricular myocardial mass end-diastolic in COPD. In addition, an increased malondialdehyde and a decreased superoxide dismutase were observed in sera of COPD patients. Mechanistically, the abundance of NOX4 and production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells could be dynamically induced by transforming growth factor-beta (TGF-β), which in turn led pulmonary arteriolar remodeling in COPD lungs.

Conclusion

These results suggest that the NOX4-derived ROS production may play a key role in the development of PH in COPD by promoting distal pulmonary vascular remodeling.
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Metadata
Title
NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD
Authors
Xiaotong Guo
Yuchun Fan
Jieda Cui
Binwei Hao
Li Zhu
Xiao Sun
Jinxi He
Jiali Yang
Jianda Dong
Yanyang Wang
Xiaoming Liu
Juan Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-018-0680-y

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