| Author | Farani, Priscila Silva Grijo´ | |
| Author | Ferreira, Beatriz Iandra da Silva | |
| Author | Begum, Khodeza | |
| Author | Pereira, Glaucia Vilar | |
| Author | Pereira, Isabela Resende | |
| Author | Fernández-Figueroa, Edith A. | |
| Author | Cardenas-Ovando, Roberto Alejandro | |
| Author | Ameida, Igor C. | |
| Author | Roy, Sourav | |
| Author | Vieira, Joseli Lannes | |
| Author | Moreira, Otacilio Cruz | |
| Access date | 2023-06-08T19:24:36Z | |
| Available date | 2023-06-08T19:24:36Z | |
| Document date | 2023 | |
| Citation | FARANI, Priscila Silva Grijó et al. Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy. PLoS Negl Trop Dis., v. 17, n.3: e0011223, p. 1 - 29, Mar. 2023. | en_US |
| ISSN | 1935-2727 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/58980 | |
| Language | eng | en_US |
| Publisher | Armando Jardim, McGill university, CANADA | en_US |
| Rights | open access | |
| Subject in Portuguese | Cardiomiopatia crônica chagásica | en_US |
| Subject in Portuguese | Tratamento com benzonidazol e A pentoxifilina | en_US |
| Subject in Portuguese | Regula o microRNA perfil transcriptômico em um modelo murino | en_US |
| Title | Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy | en_US |
| Type | Article | |
| DOI | 10.1371/ journal.pntd.0011223 | |
| Abstract | Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality
due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected
tropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized
by parasite persistence and inflammatory response in the heart tissue, which occur parallel
to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling
in the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of
benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of
both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX
treatment regimens improved electrocardiographic alterations, reducing the percentage of
mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when
compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable
changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment
groups compared with the control (infected, vehicle-treated) group. The latter showed pathways
related to organismal abnormalities, cellular development, skeletal muscle development,
cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice
exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle,
cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz
+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling
pathways related to cellular growth and proliferation, tissue development, cardiac
fibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-
5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes,
was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated.
Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed
miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment
outcomes. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular e Parasitologia. Real-Time PCR Platform RPT09A, Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular e Parasitologia. Real-Time PCR Platform RPT09A, Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Computational and Integrative Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan, Mexico City, Mexico. | en_US |
| Affilliation | Computational and Integrative Genomics, Instituto Nacional de Medicina Genómica, Arenal Tepepan, Mexico City, Mexico. | en_US |
| Affilliation | Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA. | en_US |
| Affilliation | Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular e Parasitologia. Real-Time PCR Platform RPT09A, Rio de Janeiro, RJ, Brasil | en_US |
| Subject | Chagas chronic cardiomyopathy | en_US |
| Subject | Treatment with benznidazole and pentoxifylline | en_US |
| Subject | Regulates microRNA transcriptomic profile | en_US |
| Subject | In a murine model | en_US |
