单位：[1]Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing,China北京朝阳医院[2]Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, CapitalMedical University, Beijing, China北京朝阳医院[3]Beijing Institute of Respiratory Medicine, Beijing, China北京朝阳医院[4]Department of RespiratoryDisease, Capital Medical University, Beijing, China[5]Department of Cardiac Surgery, Beijing Chao-Yang Hospital, CapitalMedical University, Beijing, China北京朝阳医院[6]Department of Pathology, Haidian Maternal & Child Health Hospital, Beijing, China[7]China-Japan Friendship Hospital, Beijing, China[8]National Clinical Research Center for Respiratory Diseases,Beijing, China
Pulmonary arterial smooth muscle cell (PASMC) migration plays a key role in vascular remodeling, which occurs during development of chronic thromboembolic pulmonary hypertension (CTEPH). Activation of the renin-angiotensin system (RAS) contributes to vascular remodeling observed in many diseases, including idiopathic pulmonary arterial hypertension. However, the role of RAS imbalance in CTEPH has not been characterized. Here, we hypothesize that RAS imbalance regulates vascular remodeling by promoting PASMC migration in CTEPH. Serum renin and angiotensin II levels in patients with CTEPH were quantified by ELISA. The pulmonary endarterectomy tissues were stained and analyzed by immunohistochemistry. PASMCs were isolated and verified by immunofluorescence staining. PASMC migration was determined by Transwell assay. Phosphorylation and protein level were detected by Western blotting. Serum levels of renin and angiotensin II were increased in patients with CTEPH {renin [median (25th percentile, 75th percentile) in pg/ml], 1,199.94 [690.85, 1,656.90] vs. 595.43 [351.48, 936.43], P < 0.001; angiotensin II [in pg/ml], 63.97 [45.97, 345.24] vs. 56.85 [11.20, 90.37], P < 0.05}. The migration of PASMCs isolated from patients with CTEPH was enhanced compared with control. Angiotensin II promoted the migration of PASMCs via activation of angiotensin II receptor 1 and phosphorylation of ERK1/2, whereas angiotensin-(1-7) counteracted this effect through activation of the Mas receptor and ERK1/2. These results demonstrate that the renin-angiotensin system regulates migration of PASMCs from patients with CTEPH via the ERK1/2 pathway. Our findings suggest that angiotensin-(1-7) or reagents targeting the renin-angiotensin system will be beneficial in the development of novel therapies for CTEPH.
基金：
fund of Key Projects in the National Science and Technology Pillar Program [2013BAI09B10]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81200041, 81300044, 81200042]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7152062]; Beijing Municipal Administration of Hospitals' Youth Programme [QML20160305]
第一作者单位：[1]Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing,China[2]Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, CapitalMedical University, Beijing, China[3]Beijing Institute of Respiratory Medicine, Beijing, China[4]Department of RespiratoryDisease, Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[2]Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, CapitalMedical University, Beijing, China[4]Department of RespiratoryDisease, Capital Medical University, Beijing, China[7]China-Japan Friendship Hospital, Beijing, China[8]National Clinical Research Center for Respiratory Diseases,Beijing, China[*1]Dept. of Respiratory Disease, Capital Medical Univ., Beijing 100069, P. R. China
推荐引用方式(GB/T 7714)：
Zhang Yun-Xia,Li Ji-Feng,Yang Yuan-Hua,et al.Renin-angiotensin system regulates pulmonary arterial smooth muscle cell migration in chronic thromboembolic pulmonary hypertension[J].AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY.2018,314(2):L276-L286.doi:10.1152/ajplung.00515.2016.
APA：
Zhang, Yun-Xia,Li, Ji-Feng,Yang, Yuan-Hua,Zhai, Zhen-Guo,Gu, Song...&Wang, Chen.(2018).Renin-angiotensin system regulates pulmonary arterial smooth muscle cell migration in chronic thromboembolic pulmonary hypertension.AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY,314,(2)
MLA：
Zhang, Yun-Xia,et al."Renin-angiotensin system regulates pulmonary arterial smooth muscle cell migration in chronic thromboembolic pulmonary hypertension".AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY 314..2(2018):L276-L286
