title: Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages.
abstract: Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4(+) T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155(-/-) mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45(+) leukocytes. Hearts of microRNA-155(-/-) mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4(+) and regulatory T cells were unchanged in miR-155(-/-) spleen proportionally, the activation of T cells and CD4(+) T cell proliferation in miR-155(-/-) mice were significantly decreased. Beyond the acute phase, microRNA-15(5-/-) mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis.
authors.affiliation: Laboratory Medicine of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Li
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Pathology of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, PR China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Suo
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, 241001, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, 241001, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lv
mesh_terms: D000818:Animals; D020868:Gene Silencing; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009205:Myocarditis / Q000503:physiopathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology*
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse