Journal
CARDIOLOGY JOURNAL
Volume 27, Issue 3, Pages 285-294Publisher
VIA MEDICA
DOI: 10.5603/CJ.a2019.0036
Keywords
miR-1; miR-133; viral myocarditis; ion channels; cell apoptosis
Categories
Funding
- National Natural Science Foundation [21728701]
- ministry of education postdoctoral fund [2015M572044]
- Shandong Province Science and Technology Development Project [GG201709260070]
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Background: The role of miR-1 and miR-133 in regulating the expression of potassium and calcium ion channels, and mediating cardiomyocyte apoptosis in mice with viral myocarditis (VMC) is investigated herein. Methods: Male Balblc mice were randomly divided into groups: control group, VMC group, VMC + + miR-1/133 mimics group, or VMC + miR-1/133 negative control (NC) group. VMC was induced with coxsackievirus B3 (CVB3). MiR-1/133 mimics ameliorated cardiac dysfunction in VMC mice and was compared to the VMC+NC group. Results: Hematoxylin and eosin staining showed a well-arranged myocardium without inflammatory cell infiltration in the myocardial matrix of the control group. However, in the VMC and VMC+NC groups, the myocardium was disorganized and swollen with necrosis, and the myocardial matrix was infiltrated with inflammatory cells. These changes were alleviated by miR- 1/133 mimics. TUNEL staining revealed decreased cardiomyocyte apoptosis in the VMC + miR-1/133 mimics group compared with the VMC group. In addition, miR-1/133 mimics up-regulated the expression of miR-1 and miR-133, the potassium channel genes Kcnd2 and Kcnj2, as well as Bcl-2, and down-regulated the expression of the potassium channel suppressor gene Irx5, L-type calcium channel subunit gene a1c (Cacna1c), Bax, and caspase-9 in the myocardium of VMC mice. MiR-1/133 also up-regulated the protein levels of Kv4.2 and Kir2.1, and down-regulated the expression of CaV1.2 in the myocardium of VMC mice. Conclusions: MiR-1 and miR-133 decreased cardiomyocyte apoptosis by mediating the expression of apoptosis-related genes in the hearts of VMC mice.
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