Activation of RhoA/Rho-kinase pathway accounts for pulmonary endothelial dysfunction in patients with chronic obstructive pulmonary disease

被引：24

作者：

Bei, Yihua ^{[1
,2
,3
]}

Duong-Quy, Sy ^{[1
]}

Hua-Huy, Thong ^{[1
]}

Dao, Pierre ^{[1
]}

Le-Dong, Nhat-Nam ^{[1
]}

Dinh-Xuan, Anh Tuan ^{[1
,2
,3
]}

机构：

[1] Paris Descartes Univ, Assistance Publ Hopitaux Paris, Hop Cochin, Med Sch,Serv Physiol,EA 2511, F-75014 Paris, France

[2] Tongji Univ, Sch Med, Clin & Translat Res Ctr, Shanghai 200120, Peoples R China

[3] Shanghai East Hosp, Shanghai 200120, Peoples R China

来源：

PHYSIOLOGICAL REPORTS | 2013年 / 1卷 / 05期

关键词：

COPD; endothelial dysfunction; eNOS; RhoA; Rho-kinases;

D O I：

10.1002/phy2.105

中图分类号：

Q4 [生理学];

学科分类号：

071003 [生理学];

摘要：

Recent evidence suggests that activation of RhoA/Rho-kinase accounts for systemic and pulmonary endothelial dysfunction in smokers with normal lung function. However, its role in patients with chronic obstructive pulmonary disease (COPD) has not yet been investigated. The aim of this study was to evaluate the regulation of RhoA/Rho-kinase pathway and pulmonary endothelial dysfunction in patients with COPD. Pulmonary arteries were obtained from nonsmokers (control subjects) and patients with nonhypoxemic and hypoxemic COPD (n = 6-7/group). Endothelium-dependent and - independent relaxations were evaluated by acetylcholine and sodium nitroprusside, respectively. Gene and protein expressions of endothelial nitric oxide synthase (eNOS) were measured by RT-PCR, Western blot, and immunohistochemistry. Nitrate, cGMP, and endothelin-1 (ET-1) concentrations, as well as Rhokinase activity were measured by ELISA. Protein expressions of total RhoA and GTP-RhoA were measured by Western blot and pull-down assay, respectively. Endothelium-dependent relaxation, and nitrate and cGMP levels were significantly reduced in pulmonary arteries of COPD patients as compared with control subjects. Conversely, activity of RhoA/Rho-kinase was increased in pulmonary arteries of COPD patients as compared with control subjects. In patients with COPD, pulmonary endothelial dysfunction was related to the downregulation of eNOS activity and upregulation of RhoA/Rho-kinase activity.

引用

页数：10

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