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FAPERJ","award":["E-26\/201\/062\/2021"],"award-info":[{"award-number":["E-26\/201\/062\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Chagas disease, the parasitic infection caused by Trypanosoma cruzi, afflicts about 6 million people in Latin America. Here, we investigated the hypothesis that T. cruzi may fuel heart parasitism by activating B1R, a G protein-coupled (brady) kinin receptor whose expression is upregulated in inflamed tissues. Studies in WT and B1R\u2212\/\u2212 mice showed that T. cruzi DNA levels (15 days post infection\u2014dpi) were sharply reduced in the transgenic heart. FACS analysis revealed that frequencies of proinflammatory neutrophils and monocytes were diminished in B1R\u2212\/\u2212 hearts whereas CK-MB activity (60 dpi) was exclusively detected in B1R+\/+ sera. Since chronic myocarditis and heart fibrosis (90 dpi) were markedly attenuated in the transgenic mice, we sought to determine whether a pharmacological blockade of the des-Arg9-bradykinin (DABK)\/B1R pathway might alleviate chagasic cardiomyopathy. Using C57BL\/6 mice acutely infected by a myotropic T. cruzi strain (Colombian), we found that daily treatment (15\u201360 dpi) with R-954 (B1R antagonist) reduced heart parasitism and blunted cardiac injury. Extending R-954 treatment to the chronic phase (120\u2013160 dpi), we verified that B1R targeting (i) decreased mortality indexes, (ii) mitigated chronic myocarditis, and (iii) ameliorated heart conduction disturbances. Collectively, our study suggests that a pharmacological blockade of the proinflammatory KKS\/DABK\/B1R pathway is cardioprotective in acute and chronic Chagas disease.<\/jats:p>","DOI":"10.3390\/jcm12082888","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T02:02:59Z","timestamp":1681696979000},"page":"2888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-3720","authenticated-orcid":false,"given":"Ana Carolina","family":"Oliveira","sequence":"first","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda Roberta Revoredo","family":"Vicentino","sequence":"additional","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Andrade","sequence":"additional","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela Resende","family":"Pereira","sequence":"additional","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8390-1266","authenticated-orcid":false,"given":"Leonardo","family":"Saboia-Vahia","sequence":"additional","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-8697","authenticated-orcid":false,"given":"Otac\u00edlio da Cruz","family":"Moreira","sequence":"additional","affiliation":[{"name":"Plataforma de PCR em Tempo Real RPT09A, Laborat\u00f3rio de Virologia Molecular, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla Eponina","family":"Carvalho-Pinto","sequence":"additional","affiliation":[{"name":"Departamento de Imunobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niter\u00f3i 24020-141, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia Barbalho da","family":"Mota","sequence":"additional","affiliation":[{"name":"Programa de Imunobiologia, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Maciel","sequence":"additional","affiliation":[{"name":"Programa de Medicina Regenerativa, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"N\u00facleo Multidisciplinar de Pesquisa em Biologia, Universidade Federal do Rio de Janeiro, Duque de Caxias Campus, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glaucia","family":"Vilar-Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o B.","family":"Pesquero","sequence":"additional","affiliation":[{"name":"Departamento de Biof\u00edsica, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseli","family":"Lannes-Vieira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia das Intera\u00e7\u00f5es, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Sirois","sequence":"additional","affiliation":[{"name":"Department of 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