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Trypanosoma cruzi Infection Induces Myocardial Nitric Oxide Synthase
H Huang Md1, J Chan Md2, M Wittner Md PhD1
1Pathology, Albert Einstein College of Medicine, Bronx, New York USA.
Insights
Chagas
Area of Science:
- Cardiology
- Immunology
- Parasitology
Background:
- Chagas' disease, caused by Trypanosoma cruzi, is a significant cause of myocarditis and cardiomyopathy.
- Myocardial dysfunction, including heart failure and arrhythmias, is linked to both acute and chronic infection.
- Nitric oxide (NO) plays a role in myocardial dysfunction in various heart diseases.
Purpose of the Study:
- To investigate the role of inducible nitric oxide synthase (iNOS) in the pathogenesis of Chagas' disease-related heart conditions.
- To examine the expression of iNOS and related cytokines in the myocardium during Trypanosoma cruzi infection.
Main Methods:
- Utilized Northern blot to detect iNOS, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA.
- Employed Western blot to assess iNOS protein expression in mouse myocardium.
- Performed immunocytochemical staining to localize iNOS expression.
- Quantified myocardial L-citrulline content as an indicator of NO production.
Main Results:
- Demonstrated significant iNOS mRNA and protein expression in the myocardium of mice infected with T. cruzi.
- Confirmed in vivo nitric oxide production through increased myocardial L-citrulline levels.
- Observed induction of IL-1β and TNF-α mRNA during the infection.
Conclusions:
- The study suggests a critical role for the myocardial cytokine-inducible nitric oxide synthase pathway in the development of Chagasic heart disease.
- This pathway represents a potential therapeutic target for pharmacological interventions against Chagas' disease complications.
Abstract:
Chagas' disease caused by Trypanosoma cruzi, is an important cause of myocarditis and cardiomyopathy. Acute and chronic infection is associated with myocardial dysfunction, including dysrhythmias, conduction disturbances, and congestive heart failure. Nitric oxide (NO) has been implicated in the myocardial dysfunction associated with diseases of the myocardium. The inducible form of nitric oxide synthase (iNOS) mediates the synthesis of NO and L-citrulline from L-arginine. An abundance of iNOS mRNA by Northern blot and a marked expression of iNOS protein by Western blot was demonstrated in the myocardium of mice 30 days postinfection with the Brazil strain of T. cruzi. Immunocytochemical staining of the myocardial sections from infected mice also revealed the expression of iNOS. Consistent with these observations, the myocardial L-citrulline content was higher in infected mice, confirming NO expression in vivo. In addition, Northern blot analysis revealed that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNA were induced during infection. These data suggest that the myocardial cytokine-iNOS pathway may be an important factor in the pathogenesis of chagasic heart disease. In addition, this pathway may be a potential target of future pharmacologic intervention.
Related Concept Videos
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Nitric Oxide Signaling Pathway
Coronary Artery Disease II: Pathophysiology
Myocarditis III: Medical Management
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Myocarditis II: Clinical Features and Diagnostic Tests

