AUTHOR=Han Junyu , Zhang Ziguan , Zhang Zhonghe , Yang Shuyu 

TITLE=Artemisinin relieves myocardial ischemia-reperfusion injury via modulating miR-29b-3p and hemicentin 1

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.918966

DOI=10.3389/fphar.2022.918966

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To explore the impact of artemisinin (ARS) on myocardial ischemia-reperfusion (I/R) injury and the underlying mechanism.</p><p><bold>Methods:</bold> Myocardial I/R rat model and cell model were used in this study. The cell viability, morphological changes, apoptosis, and oxidative stress were evaluated in cardiomyocytes H9c2 cells <italic>in vitro</italic> by using cell counting kit-8, microscope, flow cytometry, and commercial kits. High throughput sequencing is used to identify molecular targets of ARS on myocardial I/R injury, and then the gene-gene interaction network was constructed. MiR-29b-3p, hemicentin 1 (HMCN1), and apoptosis-related genes were tested by qRT-PCR and Western blotting. In the myocardial I/R rat model, echocardiography, (Triphenyl tetrazolium chloride) TTC staining, Hematoxylin-eosin (H&amp;E) staining, Masson Trichrome staining, and TUNEL staining are applied to evaluate the protective effect of ARS on the myocardial injury.</p><p><bold>Results:</bold><italic>In vitro</italic>, we demonstrated that ARS alleviated H<sub>2</sub>O<sub>2</sub>-induced myocardial I/R injury, manifested by increased H9c2 viability, decreased pathological changes, apoptosis, and oxidative stress biomarker ROS, LDH, and CK-MB. Then, sequencing analysis revealed that miR-29b-3p/HMCN1 was the target of ARS for myocardial I/R injury. Notably, rescue experiments indicated that ARS inhibited myocardial I/R injury through targeted regulation miR-29b-3p/HMCN1. <italic>In vivo</italic>, we confirmed that ARS reduced myocardial injury, fibrosis, and apoptosis <italic>via</italic> modulation of miR-29b-3p/HMCN1.</p><p><bold>Conclusion:</bold> This study demonstrated the functional role of the ARS/miR-29b-3p/HMCN1 axis in alleviating myocardial I/R injury, which provided a new direction for myocardial I/R injury therapy.</p>