NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD.
NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD.
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NOX4 表达和远端小动脉重塑与 COPD 肺动脉高压相关
DOI：
10.1186/s12890-018-0680-y
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发表时间：
2018-07-09
影响因子：
3.1
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Guo X;Fan Y;Cui J;Hao B;Zhu L;Sun X;He J;Yang J;Dong J;Wang Y;Liu X;Chen J
慢性阻塞性肺疾病(COPD)的肺动脉高压(PH)被认为是肺气肿破坏血管床和肺微环境缺氧的结果，其发病机制尚不清楚。肺血管烟酰胺腺嘌呤二核苷酸磷酸(NADPH)-加氧酶的异常表达和超氧化物的产生在缺氧性肺高压中具有重要意义。本研究通过心脏磁共振成像(CMRI)检测COPD大鼠肺血管和肺血流的形态变化，探讨NOX4在COPD肺组织中的表达及其与肺血管重构和肺功能的关系，以探讨NOX4在COPD肺小动脉重构中的作用。结果表明，在COPD肺组织中，NOX4的表达增强与肺血管壁体积增大相关。COPD患者远端肺动脉体积与主动脉扩张性、右室心肌质量、右室心肌质量呈正相关，但与肺功能呈负相关。此外，COPD患者血清中丙二醛含量升高，超氧化物歧化酶含量降低。从机制上讲，转化生长因子-β(TGFR-β)可动态诱导肺血管内皮细胞中NOX4的大量表达和活性氧(ROS)的产生，进而导致肺小动脉重构。这些结果提示，NOX4产生的ROS可能通过促进远端肺血管重塑而在COPD肺高压的发生发展中起关键作用。
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. 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 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. 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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影响因子：
3.1
作者：
Chen, I-Chen;Tan, Mian-Shin;Dai, Zen-Kong
通讯作者：
Dai, Zen-Kong
影响因子：
6.2
作者：
Lang, Roberto M.;Badano, Luigi P.;Voigt, Jens-Uwe
通讯作者：
Voigt, Jens-Uwe
影响因子：
2.5
作者：
Ibrahim, El-Sayed H.;White, Richard D.
通讯作者：
White, Richard D.
影响因子：
24
作者：
Kawut, Steven M.;Poor, Hooman D.;Parikh, Megha A.;Hueper, Katja;Smith, Benjamin M.;Bluemke, David A.;Lima, Joao A. C.;Prince, Martin R.;Hoffman, Eric A.;Austin, John H. M.;Vogel-Claussen, Jens;Barr, Graham
通讯作者：
Barr, Graham
小气道平滑肌中NOX4的表达与COPD病情严重程度相关
影响因子：
--
作者：
Liu X;Hao B;Ma A;He J;Liu X;Chen J
通讯作者：
Chen J