Key result
Trypanosoma cruzi infection in mice led to a 54-60% decline in cardiac mtDNA content and a 37-50% reduction in OXPHOS-mediated ATP synthesis capacity.
Chagasic cardiomyopathy development in a murine model is associated with significant mitochondrial dysfunction, including respiratory chain complex deficiencies and reduced ATP synthesis capacity, supporting a free radical hypothesis.
Mitochondrial dysfunction may drive energy failure in murine Chagas cardiomyopathy; hypothesis-generating for human mechanisms and targets.
In this study, we evaluated the activities of respiratory chain complexes and oxidative phosphorylation (OXPHOS) capacity of the heart to gain insights into the pathological significance of mitochondrial dysfunction in chagasic cardiomyopathy (CCM). In a murine model of Trypanosoma cruzi infection, biochemical and histochemical analysis of the cardiac mitochondria revealed deficiency of the respiratory chain complexes (CI-CV) in infected mice; the inhibition of CI activity was more pronounced in the acute infection phase, CIII was constitutively repressed throughout the infection and disease phase, and the CV defects appeared in chronic phase only. A substantial decline in cardiac mtDNA content (54-60%) and mitochondria-encoded transcripts (50-65%) with disease development indicated that the alterations in mtDNA contribute to the quantitative deficiencies in respiratory chain activity in chagasic hearts. The observations of a selective inhibition of redox-sensitive CI and CIII complexes that are also the site of free radical generation in mitochondria, and the decline in cardiac mtDNA content in infected mice, all support the free radical hypothesis of mitochondria dysfunction in CCM. Consequently, OXPHOS-mediated ATP synthesis capacity of the cardiac mitochondria in infected mice was substantially reduced (37-50%), suggesting an energy homeostasis in the affected tissue.
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Vyatkina et al. (2004) studied Chagasic cardiomyopathy. Trypanosoma cruzi infection vs. Uninfected mice (implied) was evaluated on Activities of respiratory chain complexes, oxidative phosphorylation capacity, and mtDNA content. Trypanosoma cruzi infection in mice led to a 54-60% decline in cardiac mtDNA content and a 37-50% reduction in OXPHOS-mediated ATP synthesis capacity.
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