ArticleJournal of the American Heart Association2012
Defects of mtDNA replication impaired mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and chagasic patients: the role of Nrf1/2 and antioxidant response.
Article in Journal of the American Heart Association, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023.Arquivos brasileiros de cardiologia · 2023Guideline
- Nuclear Respiratory Factor-1 Ameliorates Heart Failure by Suppressing Cardiomyocyte Pyroptosis-Associated Signaling Via the Downregulation of Gasdermin D and Caspase-1.Cardiology research · 2026Article
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
- PARP1-NFATc1-PD1 pathway of maturation and stability of CD8iScience · 2025Article
- Heart function enhancement by an Nrf2-activating antioxidant in acute Y-strain Chagas disease, but not in chronic Colombian or Y-strain.PLoS neglected tropical diseases · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Chagas Disease Megaesophagus Patients Carrying VariantBiomedicines · 2022Article
- The Role of Mitochondrial Quality Control in Anthracycline-Induced Cardiotoxicity: From Bench to Bedside.Oxidative medicine and cellular longevity · 2022Review
- Xeno-free workflow exhibits comparable efficiency and quality of keratinocytes isolated from human skin biopsies.Regenerative therapy · 2021Article
- Oxidative stress implications for therapeutic vaccine development against Chagas disease.Expert review of vaccines · 2021Review
- Mitochondria as a Cellular Hub in Infection and Inflammation.International journal of molecular sciences · 2021Review
- Prognostic Performance of Peripheral Blood Biomarkers in Identifying Seropositive Individuals at Risk of Developing Clinically Symptomatic Chagas Cardiomyopathy.Microbiology spectrum · 2021Article
- Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease.Journal of clinical immunology · 2021Article
- The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells.Frontiers in pharmacology · 2021Article
- The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors.Oxidative medicine and cellular longevity · 2021Review
- Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy.Frontiers in immunology · 2021Article
- Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.Frontiers in immunology · 2021Article
- Transcriptional Studies onFrontiers in cellular and infection microbiology · 2021Review
- Sirtuin Control of Mitochondrial Dysfunction, Oxidative Stress, and Inflammation in Chagas Disease Models.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)-regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. METHODS AND
resultsWe utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi-infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)-regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts.
conclusionsThe replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi-infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease.
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Registered trials
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