ArticlePLoS neglected tropical diseases2012
Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Kinetics of Biomarkers for Therapeutic Assessment in Swiss Mice Infected with a VirulentPathogens (Basel, Switzerland) · 2026Article
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
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- NMDA receptor remodeling and nNOS activation in mice after unilateral striatal injury with 6-OHDA.Heliyon · 2024Article
- Exclusion of Horizontal and Vertical Transmission as Major Sources ofComparative medicine · 2023Article
- Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy.PLoS neglected tropical diseases · 2023Article
- Immunopathological Mechanisms Underlying Cardiac Damage in Chagas Disease.Pathogens (Basel, Switzerland) · 2023Review
- Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.PLoS neglected tropical diseases · 2022Article
- Insights from the use of erythropoietin in experimental Chagas disease.International journal for parasitology. Drugs and drug resistance · 2022Article
- Admixture mapping analysis reveals differential genetic ancestry associated with Chagas disease susceptibility in the Colombian population.Human molecular genetics · 2021Article
- High variation in immune responses and parasite phenotypes in naturally acquired Trypanosoma cruzi infection in a captive non-human primate breeding colony in Texas, USA.PLoS neglected tropical diseases · 2021Article
- CCL3/Macrophage Inflammatory Protein-1α Is Dually Involved in Parasite Persistence and Induction of a TNF- and IFNγ-Enriched Inflammatory Milieu inFrontiers in immunology · 2020Article
- TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas' heart disease.PLoS neglected tropical diseases · 2019Article
- Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice.Mediators of inflammation · 2019Article
- Genetic Polymorphism atFrontiers in immunology · 2018Article
- Role of Inactive and ActiveFrontiers in microbiology · 2017Article
- Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease.Antimicrobial agents and chemotherapy · 2016Article
- Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease.PLoS neglected tropical diseases · 2016Article
- Down regulation of NO signaling in Trypanosoma cruzi upon parasite-extracellular matrix interaction: changes in protein modification by nitrosylation and nitration.PLoS neglected tropical diseases · 2015Article
- Pentoxifylline reverses chronic experimental Chagasic cardiomyopathy in association with repositioning of abnormal CD8+ T-cell response.PLoS neglected tropical diseases · 2015Article
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Authors and funding
12 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/-)) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/-) mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+) cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue.
resultsChronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+) cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/-) mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue.
conclusionT. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC severity, mainly disturbing of the molecular pathway involved in electrical synchrony. These findings open a new avenue for therapeutic tools in Chagas' heart disease.
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