Myocarditis is associated with cardiac inflammation due to infection of the myocardium and may lead to dilated cardiomyopathy. Viral infection promotes macrophage infiltration, oxidative stress, and expression of pro-inflammatory cytokines and microRNAs (miRNAs). Numerous miRNAs play a role in myocarditis-induced cardiomyopathy, however, sex differences in the miRNA expression in chronic myocarditis remain unknown.

In the present study, male and female ABY/SnJ mice were infected with coxsackievirus B3 (CVB3). After 28 days, cardiac tissue was used for real-time PCR and western blot analysis. Pro-inflammatory markers (e.g., TNF-α, IL-1β, iNOS, TLR4, MCP-1, c-fos and osteopontin (OPN)) as well as inflammation- and remodelling-related miRNAs were analysed in the cardiac tissue of infected and control mice.

Chronic CVB3-related myocardial infection promoted cardiac hypertrophy. In addition, male CVB3 mice showed a significant reduction in body weight. CVB3-infected mice showed an increased number of immune cell infiltrates in myocardial tissue than non-infected mice 28 days after infection. Moreover, mice with chronic myocarditis showed higher amounts of pathological fibrosis in comparison to uninfected mice, having only male hearts more fibrotic tissue. Col1A1 and Col3A1 expression was similar in the hearts of mice with chronic myocarditis and the control group however, in the female CVB3-myocarditis group, the OPN mRNA expression was significantly higher in females from the CVB3-myocarditis group. The pro-inflammatory factor NFκB remained unaltered in both male and female CVB3-myocarditis groups. The mRNA levels of the pro-inflammatory markers TNF-α, IL-1β, iNOS, TLR4 and MCP-1 were elevated in CVB3-myocarditis male mice in comparison to the male control group, whereas these factors were not elevated in CVB3-infected females. Sex differences in the expression of pro-inflammatory markers were observed in mice with chronic myocarditis.

In conclusion, our results suggest a sex-specific expression of pro-inflammatory markers as well as inflammation-related miRNAs with higher pro-inflammatory response in male CVB3 chronic myocarditis mice.