title: Activation of RhoA/Rho-kinase pathway accounts for pulmonary endothelial dysfunction in patients with chronic obstructive pulmonary disease.
abstract: 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 Rho-kinase 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.
authors.affiliation: Medical School, Assistance Publique Hôpitaux de Paris, Service de Physiologie, Paris Descartes University EA 2511, Hôpital Cochin, 27 Rue du faubourg Saint-Jacques, 75014, Paris, France ; Clinical and Translational Research Center, Tongji University School of Medicine and Shanghai East Hospital 150 Jimo Road, Shanghai, 200120, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.forename: Sy
authors.initials: S
authors.lastname: Duong-Quy
authors.forename: Thong
authors.initials: T
authors.lastname: Hua-Huy
authors.forename: Pierre
authors.initials: P
authors.lastname: Dao
authors.forename: Nhat-Nam
authors.initials: NN
authors.lastname: Le-Dong
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Dinh-Xuan
keywords: COPD; Rho-kinases; RhoA; eNOS; endothelial dysfunction