J-L Bao1, L Lin. 1. Department of Internal Medicine, Zaozhuang Municipal Hospital, Zaozhuang, Shangdong Province, P.R. China. baojinli410@163.com.
Abstract
OBJECTIVES: Acute viral myocarditis (VM) is an important cause of sudden cardiac death and heart failure in healthy young person. Its pathogenesis is based on an adverse immune response evoked by infection of the cardiac muscle by cardiotropic viruses especially Coxackievirus B3 (CVB3). MicroRNAs (miRNAs) are short, noncoding RNA sequences that regulate gene expression at the posttranscriptional level. Recently, there are reports that disturbed miRNAs expression is associated with VM but the mechanism is not well understood. MATERIALS AND METHODS: Herein, we screened 15 selected miRNAs in myocardial tissues of patients with acute CVB3 caused myocarditis and found the expression of miR-155 and miR-148a was up-regulated significantly. RESULTS: Predicted by using bioinformatics tools and confirmed by dual-luciferase assay and western blot, we confirmed that RelA is a direct target gene of miR-155 and miR-148a. Subsequent in vitro functional study indicated that miR-155 function as immune response negative feedback factor that reduced cardiac myoblast cytokines expression during CVB3 infection. Further in vivo experiments indicated that miR-155 can improved mice survival rate when CVB3 infected. CONCLUSIONS: So, our study indicated that miR-155 is a potential therapeutic target for viral myocarditis.
OBJECTIVES: Acute viral myocarditis (VM) is an important cause of sudden cardiac death and heart failure in healthy young person. Its pathogenesis is based on an adverse immune response evoked by infection of the cardiac muscle by cardiotropic viruses especially Coxackievirus B3 (CVB3). MicroRNAs (miRNAs) are short, noncoding RNA sequences that regulate gene expression at the posttranscriptional level. Recently, there are reports that disturbed miRNAs expression is associated with VM but the mechanism is not well understood. MATERIALS AND METHODS: Herein, we screened 15 selected miRNAs in myocardial tissues of patients with acute CVB3 caused myocarditis and found the expression of miR-155 and miR-148a was up-regulated significantly. RESULTS: Predicted by using bioinformatics tools and confirmed by dual-luciferase assay and western blot, we confirmed that RelA is a direct target gene of miR-155 and miR-148a. Subsequent in vitro functional study indicated that miR-155 function as immune response negative feedback factor that reduced cardiac myoblast cytokines expression during CVB3 infection. Further in vivo experiments indicated that miR-155 can improved mice survival rate when CVB3 infected. CONCLUSIONS: So, our study indicated that miR-155 is a potential therapeutic target for viral myocarditis.
Authors: Sribalasubashini Muralimanoharan; Cun Li; Ernesto S Nakayasu; Cameron P Casey; Thomas O Metz; Peter W Nathanielsz; Alina Maloyan Journal: J Mol Cell Cardiol Date: 2017-06-19 Impact factor: 5.000