{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:47:57Z","timestamp":1778600877193,"version":"3.51.4"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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)-1\u03b1 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-1\u03b1 and CD73 expression. Moreover, the number of HIF-1\u03b1+ 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.<\/jats:p>","DOI":"10.1002\/jlb.4ma0420-125r","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T22:24:20Z","timestamp":1590445460000},"page":"233-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["HIF-1\u03b1 and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end-stage Chagas disease patients"],"prefix":"10.1093","volume":"109","author":[{"given":"Natalia","family":"Eberhardt","sequence":"first","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET) , C\u00f3rdoba , Argentina"},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana Maria","family":"Sanmarco","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET) , C\u00f3rdoba , Argentina"},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba , Argentina"},{"name":"Brigham and Women\u2019s Hospital, Department of Neurology, Harvard Institute of Medicine , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gast\u00f3n","family":"Bergero","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), Consejo Nacional de Investigaciones 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Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-7702","authenticated-orcid":true,"given":"Maria Pilar","family":"Aoki","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET) , C\u00f3rdoba , Argentina"},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"2023032108383239700_jlb10678-cit-0001","doi-asserted-by":"crossref","first-page":"1251 e7-9","DOI":"10.1016\/j.amjmed.2015.04.036","article-title":"Chagas heart disease: an update","volume":"128","author":"Malik","year":"2015","journal-title":"Am J 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