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Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: molecular genetic evidence
- Source :
- Clinical Science. 103:263S-266S
- Publication Year :
- 2002
- Publisher :
- Portland Press Ltd., 2002.
-
Abstract
- Trypanosoma cruzi is the aetiological agent of Chagas' disease, an important cause of chronic cardiomyopathy. We previously demonstrated a role for endothelin-1 (ET-1) in the pathogenesis of chagasic heart disease. In order to explore further the significance of ET-1 in chagasic heart disease, we infected ET-1 (flox/flox); alpha-MHC-Cre(+) (ET-1KO) mice, in which the ET-1 gene has been deleted from cardiac myocytes, with 10(4) T. cruzi (Brazil strain) trypomastigotes. As controls, we used ET-1 (flox/flox);Cre(-) (FLOX) and C57BL/6x129sv (WT) mice. All mice survived and were evaluated 150-160 days post-infection. Cardiac magnetic resonance imaging revealed a significant increase in right ventricular internal diameter in all infected animals except ET-1KO mice (control WT, 1.6+/-0.10 mm; infected WT, 2.8+/-0.15 mm; control FLOX, 2.04+/-0.02 mm; infected FLOX, 2.76+/-0.28 mm). There was no significant difference in right ventricular internal diameter between infected and uninfected ET-1KO mice (control ET-1KO, 1.83+/-0.11 mm; infected ET-1KO, 2.14+/-0.20 mm). In another series of experiments, transthoracic echocardiography was performed on uninfected as well as infected ET-1KO mice, and uninfected and infected FLOX mice. Both infected groups had an increased left ventricular end-diastolic diameter and reduced fractional shortening. In addition, relative wall thickness was also decreased in infected animals. However, the magnitude of these changes was less in infected ET-1KO mice. These data provide further support for a role for ET-1 in the pathogenesis of chronic chagasic heart disease, and indicate that cardiac myocytes are an important source of ET-1 in this disease.
- Subjects :
- Chagas Cardiomyopathy
Male
Mice, Knockout
Chagas disease
Pathology
medicine.medical_specialty
Endothelin-1
Heart disease
Myocardium
Cardiomyopathy
General Medicine
Biology
medicine.disease
biology.organism_classification
Magnetic Resonance Imaging
Endothelin 1
Pathogenesis
Mice
Echocardiography
FLOX
medicine
Animals
Myocyte
Trypanosoma cruzi
Subjects
Details
- ISSN :
- 01435221
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Clinical Science
- Accession number :
- edsair.doi.dedup.....b34acaaf3448af62b5cfeb95f0d8e16a
- Full Text :
- https://doi.org/10.1042/cs103s263s