Related Experiment Videos
Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice
H Nakamura1, T Yamamoto, T Yamamura
1The Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Insights
Repetitive coxsackievirus B3 infection in mice led to cardiac dilatation without inflammation. Autoimmunity may drive this, suggesting viral infections contribute to heart dilation.
Area of Science:
- Cardiology
- Virology
- Immunology
Background:
- The relationship between myocarditis and dilated cardiomyopathy (DCM) remains unclear.
- Understanding the pathogenic mechanisms is crucial for treating these conditions.
Purpose of the Study:
- To investigate the effect of repetitive coxsackievirus B3 (CVB3) inoculation on post-myocarditic mice.
- To clarify the role of viral infections and autoimmunity in cardiac dilatation.
Main Methods:
- Inbred A/J mice were inoculated with CVB3 and reinfected at 40 weeks.
- Cardiac function, histology, and molecular markers were assessed.
- Electron microscopy and antibody staining were used to analyze cardiac tissue.
Main Results:
- Repetitive CVB3 infection caused significant cardiac enlargement and left ventricular dilatation.
- Left and right ventricular free walls thinned, and sarcomere length increased.
- Increased IgM antibody staining and TNF-alpha levels were observed without significant inflammation or fibrosis.
Conclusions:
- Repetitive CVB3 infection can induce cardiac dilatation in post-myocarditic mice without overt inflammation.
- Autoimmunity, potentially mediated by antibodies against viral components, may play a role in the pathogenesis of cardiac dilatation.
- Recurrent viral infections could contribute to the development of dilated cardiomyopathy.
Abstract:
The relation between mycarditis and dilated cardiomyopathy (DCM) is controversial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2x10(4) plaque-forming units) and reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ group were significantly increased compared with those of the 3W-/40W+ group, and both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other groups. No increase in inflammatory cell infiltration or fibrosis progression was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but the second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31+/-0.20 mm vs 2.61+/-0.19 mm, p<0.05; 0.54+/-0.09 mm vs 0.72+/-0.16 mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microscopy. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of TNF-alpha in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflammatory cell infiltration in post- myocarditic mice. Autoimmunity mediated by the circulation of certain antibodies (eg, antibodies against the CVB3 genome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation.