Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis

doi:10.1097/FJC.0000000000001271

科研成果详情

题名	Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis
作者	Cai, Haijian 1; Fan, Shiqian 1,2; Cai, Luqiong 1; Zhu, Lin 1; Zhao, Zhucheng 1; Li, Yaozhe 1; Yao, Yizhu 1; Huang, Xiaoying 1; Wang, Liangxing1
发表日期	2022-07
发表期刊	JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	dihydroartemisinin pulmonary hypertension hypoxia MiR-503 ELAVL2
其他关键词	RNA-BINDING PROTEINS ; ARTESUNATE ; INHIBITION ; PATHWAY ; HUR
摘要	Dihydroartemisinin (DHA) is an active form of artemisinin extracted from the traditional Chinese medicine Artemisia annua, which is used to treat malaria. Previous studies have shown that DHA has a therapeutic effect on pulmonary hypertension (PH), but its specific mechanism has not been fully elucidated. In this study, a hypoxia-induced PH mouse model was established and DHA was administered as a therapeutic intervention. We measured hemodynamics and right ventricular hypertrophy and observed hematoxylin and eosin staining of lung tissue sections, proving the therapeutic effect of DHA on PH. Furthermore, cell counting kit-8 and 5-ethynyl-2 '-deoxyuridine (EdU) cell proliferation assay kit were performed to examine cell proliferation of pulmonary artery smooth muscle cells cultured in hypoxia or in normoxia. Transwell migration chamber assay was performed to examine cell migration of the same cell model. Consistent with the therapeutic effect in vivo, DHA inhibited hypoxia-induced cell proliferation and migration. Through high-throughput sequencing of mouse lung tissue, we screened embryonic lethal abnormal vision-like 2 (ELAVL2) as a key RNA binding protein in PH. Mechanistically, DHA inhibited the proliferation and migration of pulmonary artery smooth muscle cells by promoting the expression of ELAVL2 and regulating the miR-503/PI3K/AKT pathway. The binding relationship between ELAVL2 and pre-miR-503 was verified by RNA binding protein immunoprecipitation assay. In conclusion, we first propose that DHA alleviates PH through the ELAVL2/miR-503/PI3K/AKT pathway, which may provide a basis for new therapeutic strategies of PH.
资助项目	Key Laboratory of Heart and Lung of Wenzhou Medical University
出版者	LIPPINCOTT WILLIAMS & WILKINS
出版地	PHILADELPHIA
ISSN	0160-2446
EISSN	1533-4023
卷号	80 期号:1 页码:95-109
DOI	10.1097/FJC.0000000000001271
页数	15
WOS类目	Cardiac & Cardiovascular Systems ; Pharmacology & Pharmacy
WOS研究方向	Cardiovascular System & Cardiology ; Pharmacology & Pharmacy
WOS记录号	WOS:000821237600010
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35512032
SCOPUSEID	2-s2.0-85134360488
通讯作者地址	[Huang, Xiaoying]Division of Pulmonary Medicine,The First Affiliated Hospital of Wenzhou Medical University,Key Laboratory of Heart and Lung,Zhejiang,Wenzhou,China ; [Wang, Liangxing]Division of Pulmonary Medicine,The First Affiliated Hospital of Wenzhou Medical University,Key Laboratory of Heart and Lung,Zhejiang,Wenzhou,China
Scopus学科分类	Pharmacology;Cardiology and Cardiovascular Medicine
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/154454
专题	附属第一医院其他_附属义乌医院（义乌市中心医院）
通讯作者	Huang, Xiaoying; Wang, Liangxing
作者单位	1.Division of Pulmonary Medicine,The First Affiliated Hospital of Wenzhou Medical University,Key Laboratory of Heart and Lung,Zhejiang,Wenzhou,China; 2.Yiwu Hospital Affiliated to Wenzhou Medical University (Yiwu Municipal Central Hospital),Zhejiang,Yiwu,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Cai, Haijian,Fan, Shiqian,Cai, Luqiong,et al. Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis[J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,2022,80(1):95-109.
APA	Cai, Haijian., Fan, Shiqian., Cai, Luqiong., Zhu, Lin., Zhao, Zhucheng., ... & Wang, Liangxing. (2022). Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 80(1), 95-109.
MLA	Cai, Haijian,et al."Dihydroartemisinin Attenuates Hypoxia-Induced Pulmonary Hypertension Through the ELAVL2/miR-503/PI3K/AKT Axis".JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 80.1(2022):95-109.