title: Salidroside exerts protective effects against chronic hypoxia-induced pulmonary arterial hypertension via AMPKα1-dependent pathways.
abstract: Salidroside, an active ingredient isolated from Rhodiola rosea, has shown to exert protective effects against chronic hypoxia-induced pulmonary arterial hypertension (PAH). However, the underlying mechanisms were not well known. Based on our recent reports, we predicted the involvement of adenosine monophosphate-activated protein kinase (AMPK) mediated effects in salidroside regulation of PAH. Firstly, to prove the hypothesis, rats were exposed to chronic hypoxia and treated with increasing concentrations of salidroside or a selective AMPK activator-5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) for 4 weeks. After salidroside or AICAR treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary artery remodeling were attenuated. Then the effects of salidroside or AICAR on hypoxia-induced excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs), which contributed to pulmonary arterial remodeling, were investigated. Our results suggested salidroside, as well as AICAR, reversed hypoxia-induced PASMCs proliferation and apoptosis resistance while AMPK inhibitor Compound C enhanced the effects of hypoxia. To reveal the potential cellular mechanisms, activation of AMPKα1 and expression of the genes related to proliferation and apoptosis were analyzed in PASMCs after salidroside treatment under hypoxia conditions. The results demonstrated salidroside as well as AICAR might inhibit chronic hypoxia-induced PASMCs proliferation via AMPKα1-P53-P27/P21 pathway and reverse apoptosis resistance via AMPKα1-P53-Bax/Bcl-2-caspase 9-caspase 3 pathway.
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: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Radiology, First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Chang
authors.initials: C
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: Peiliang
authors.initials: P
authors.lastname: Wu
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: Yangyang
authors.initials: Y
authors.lastname: Fu
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: Rong
authors.initials: R
authors.lastname: Fan
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: Cunlai
authors.initials: C
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: Liangxing
authors.initials: L
authors.lastname: Wang
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: Xiaoying
authors.initials: X
authors.lastname: Huang
keywords: AMPKα1; Salidroside; apoptosis; proliferation; pulmonary arterial hypertension