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Captopril suppresses interstitial fibrin deposition in coxsackievirus B3 myocarditis
H Takada1, C Kishimoto, Y Hiraoka
1Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Abstract:
The effects of captopril on murine coxsackievirus B3 (CB3) myocarditis were investigated, with focus on interstitial fibrin deposition and changes in the connective tissue matrix. Captopril was administered intraperitoneally at a dose of 0.1 mg/g to CB3-infected mice daily on days 10-30 in experiment I (inflammatory phase) and on days 30-60 in experiment II (fibrotic phase). In experiment I, mouse survival was higher in the captopril-treated group than in the untreated group. Histological improvement, including prevention of extravasated fibrin deposition, maintenance of connective tissue architecture, suppression of myocyte hypertrophy, and prevention of myosin isoform shift from alpha to beta, was observed in captopril-treated mice in experiment I, but not in experiment II; in experiment II, captopril administration suppressed thickening of the interstitial reticulin fibers. Captopril inhibited inflammatory fibrin deposition, postmyocarditic myocyte hypertrophy, and ventricular remodeling during the inflammatory phase, but not during the fibrotic phase, of CB3 myocarditis in mice.
Insights
Captopril improved survival and reduced inflammation in coxsackievirus B3 (CB3) myocarditis during the early inflammatory phase. However, it did not prevent fibrosis or ventricular remodeling during the later fibrotic phase.
Area of Science:
- Cardiology
- Virology
- Pharmacology
Background:
- Coxsackievirus B3 (CB3) myocarditis is a significant cause of heart disease.
- Interstitial fibrin deposition and connective tissue matrix changes characterize CB3 myocarditis.
- Understanding therapeutic interventions for myocarditis is crucial.
Purpose of the Study:
- To investigate the effects of captopril on CB3-induced myocarditis in mice.
- To assess captopril's impact on fibrin deposition and connective tissue remodeling.
- To determine efficacy during different phases of myocarditis.
Main Methods:
- Murine model of coxsackievirus B3 myocarditis.
- Captopril administration during the inflammatory (days 10-30) and fibrotic (days 30-60) phases.
- Histological analysis focusing on fibrin deposition, connective tissue, myocyte hypertrophy, and myosin isoforms.
Main Results:
- Captopril treatment increased survival rates during the inflammatory phase.
- Histological improvements observed in the inflammatory phase: reduced fibrin, preserved architecture, suppressed hypertrophy, and prevented myosin shift.
- Captopril suppressed interstitial reticulin fiber thickening in the fibrotic phase but did not reverse established changes.
Conclusions:
- Captopril demonstrates beneficial effects during the inflammatory phase of CB3 myocarditis, improving survival and mitigating key pathological features.
- Captopril's efficacy is phase-dependent, with limited impact on established fibrosis and remodeling in the later stages.
- These findings suggest captopril may be a valuable therapeutic option for early-stage viral myocarditis.