title: Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway.
abstract: Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial remodeling mainly due to excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Salidroside, an active ingredient isolated from Rhodiola rosea is proposed to exert protective effects against PAH. However, the function of salidroside in PAH has not been investigated systematically and the underlying mechanisms are not clear. To investigate the effects of salidroside on PAH, the mice in chronic hypoxia model of PAH were given by an increasing concentration of salidroside (0, 16 mg/kg, 32 mg/kg, and 64 mg/kg). After salidroside treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary arterial remodeling were attenuated, suggesting a protective role played by salidroside in PAH. To explore the potential mechanisms, the apoptosis of PASMCs after salidroside treatment under hypoxia conditions were determined in vivo and in vitro, and also the mitochondria-dependent apoptosis factors, Bax, Bcl-2, cytochrome C, and caspase 9 were examined. The results revealed that salidroside reversed hypoxia-induced cell apoptosis resistance at least partially via a mitochondria-dependent pathway. In addition, salidroside upregulated the expression of adenosine A2a receptor (A2aR) in lung tissues of mice and in PASMCs in vitro after hypoxia exposure. Combined the evidence above, we conclude that salidroside can attenuate chronic hypoxia-induced PAH by promoting PASMCs apoptosis via an A2aR related mitochondria dependent pathway.
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.. Electronic address: drhuangxy@163.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Zou
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Mayun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Yanfan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ding
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
authors.forename: Xueding
authors.initials: X
authors.lastname: Cai
authors.affiliation: Division of Pulmonary Medicine First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.. Electronic address: wzyxywlx@163.com.
authors.forename: Liangxing
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D066253:Vascular Remodeling
chemical_list: D005960:Glucosides; D010636:Phenols; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; C009172:rhodioloside
keywords: Adenosine A(2a) receptor; Apoptosis; Chronic hypoxia; Pulmonary arterial hypertension; Salidroside