HIF-1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end-stage Chagas disease patients
| Autor: | Roberto R. Favaloro, Carlos Vigliano, Liliana Maria Sanmarco, Natalia Eberhardt, Maria del Pilar Aoki, Gastón Bergero |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chagas disease Adult Chagas Cardiomyopathy Male Myocarditis medicine.medical_treatment Immunology Cardiomyopathy Biology GPI-Linked Proteins Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system medicine Leukocytes Immunology and Allergy Humans 5'-Nucleotidase Heart transplantation Myocardium Purinergic receptor Cell Biology Middle Aged medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit 030104 developmental biology 030220 oncology & carcinogenesis Heart failure Female |
| Zdroj: | Journal of leukocyte biologyREFERENCES. 109(1) |
| ISSN: | 1938-3673 |
| Popis: | Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% of Trypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads to ventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end-stage Chagas disease patients. Although the pathophysiology of Chagas disease has been addressed for decades by numerous groups, the cardiac immunologic mechanisms involved in the progression of clinical manifestation are still unknown. Growing evidence demonstrates that hypoxia-inducible factor (HIF)-1α plays indispensable roles in driving immune response by triggering the expression of CD73 purinergic ecto-enzyme. Purinergic system controls the duration and magnitude of purine signals directed to modulate immune cells through the conversion of extracellular ATP (microbicide/proinflammatory) to the immunoregulatory metabolite adenosine. In the present work, we described that infiltrating leukocytes within cardiac explants from patients with end-stage Chagas cardiomyopathy up-regulated HIF-1α and CD73 expression. Moreover, the number of HIF-1α+ and CD73+ leukocytes positively correlated with the myocarditis severity and the local parasite load. Furthermore, we demonstrated a direct relationship between tissue parasite persistence and the influx of immune cells to the infected hearts, which ultimately determine the severity of the myocarditis. These findings provide evidence that CD73-dependent regulatory pathways are locally triggered in the myocardium of patients with end-stage Chagas disease. |
| Databáze: | OpenAIRE |
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