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Myocardial expression of endothelin-1 in murine Trypanosoma cruzi infection
S B Petkova1, H B Tanowitz, H I Magazine
1Departments of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Insights
Chagas disease infection increases endothelin-1 (ET-1) in the cardiovascular system. This contributes to myocardial dysfunction and inflammation during acute infection.
Area of Science:
- Cardiovascular Science
- Infectious Diseases
- Molecular Biology
Background:
- Chagas' disease, caused by Trypanosoma cruzi, leads to myocarditis and cardiomyopathy.
- Previous work showed Trypanosoma cruzi infection elevates endothelin-1 (ET-1) synthesis in endothelial cells.
Purpose of the Study:
- To investigate the role of ET-1 in the cardiovascular system during acute Chagas' disease infection in mice.
- To determine if ET-1 expression and levels are altered following Trypanosoma cruzi infection.
Main Methods:
- Infection of CD1 and C57BL/6 mice with different strains of Trypanosoma cruzi.
- Histopathological examination of cardiac tissues for myonecrosis, pseudocysts, and vasculitis.
- Immunohistochemistry to detect ET-1 expression in endothelial cells.
- Quantitative analysis of mRNA levels for preproET-1 and endothelin converting enzyme.
- Measurement of plasma ET-1 levels.
Main Results:
- Infected mice exhibited myonecrosis, pseudocysts, and vasculitis in the aorta, coronary arteries, and myocardial vessels.
- Increased ET-1 expression was observed, particularly in the endocardial and vascular endothelium.
- Elevated mRNA levels for preproET-1, endothelin converting enzyme, and ET-1 were found in myocardial samples.
- Plasma ET-1 levels were significantly increased in infected mice 10-15 days post-infection.
Conclusions:
- Increased endothelin-1 (ET-1) is a direct consequence of Trypanosoma cruzi invasion of the cardiovascular system.
- Elevated ET-1 provides a potential mechanism for the myocardial dysfunction observed in Chagas' disease.
- The findings highlight ET-1 as a key mediator in the pathogenesis of infection-associated cardiovascular complications.
Abstract:
Chagas' disease, caused by Trypanosoma cruzi, is an important cause of myocarditis and chronic cardiomyopathy and is accompanied by microvascular spasm and myocardial ischemia. We reported previously that infection of cultured endothelial cells with T. cruzi increased the synthesis of biologically active endothlein-1 (ET-1). In the present study, we examined the role of ET-1 in the cardiovascular system of CD1 mice infected with the Brazil strain of T. cruzi and C57BL/6 mice infected with the Tulahuen strain during acute infection. In the myocardium of infected mice myonecrosis and multiple pseudocysts were observed. There was also an intense vasculitis of the aorta, coronary artery, smaller myocardial vessels and the endocardial endothelium. Immunohistochemistry studies employing anti-ET-1 antibody revealed increased expression of ET-1 that was most intense in the endocardial and vascular endothelium. Elevated levels of mRNA for preproET-1, endothelin converting enzyme and ET-1 were observed in the same myocardial samples. Plasma ET-1 levels were significantly elevated in infected CD1 mice 10-15 days post infection. These observations suggest that increased levels of ET-1 are a consequence of the initial invasion of the cardiovascular system and provide a mechanism for infection-associated myocardial dysfunction.