Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses
Abstract Background Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (...
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Online Access: | https://doi.org/10.1186/s41182-023-00552-6 https://doaj.org/article/3e5f69651e364dbbadcb1df0304f3316 |
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ftdoajarticles:oai:doaj.org/article:3e5f69651e364dbbadcb1df0304f3316 2024-01-14T10:04:58+01:00 Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses Katherine-Sofia Candray-Medina Yu Nakagama Masamichi Ito Shun Nakagama Evariste Tshibangu-Kabamba Norihiko Takeda Yuki Sugiura Yuko Nitahara Yu Michimuko-Nagahara Natsuko Kaku Yoko Onizuka Carmen-Elena Arias Maricela Mejia Karla Alas Susana Peña Yasuhiro Maejima Issei Komuro Junko Nakajima-Shimada Yasutoshi Kido 2023-12-01T00:00:00Z https://doi.org/10.1186/s41182-023-00552-6 https://doaj.org/article/3e5f69651e364dbbadcb1df0304f3316 EN eng BMC https://doi.org/10.1186/s41182-023-00552-6 https://doaj.org/toc/1349-4147 doi:10.1186/s41182-023-00552-6 1349-4147 https://doaj.org/article/3e5f69651e364dbbadcb1df0304f3316 Tropical Medicine and Health, Vol 51, Iss 1, Pp 1-17 (2023) Trypanosoma cruzi Chagas disease Transcriptome HL-1 In vitro modeling Dilated cardiomyopathy Arctic medicine. Tropical medicine RC955-962 article 2023 ftdoajarticles https://doi.org/10.1186/s41182-023-00552-6 2023-12-17T01:47:19Z Abstract Background Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (CCM) progression. Our objective was to elucidate the differential transcriptomic signatures of cardiomyocytes resulting from infection with genetically discrete T. cruzi strains and explore their relationships with CCM pathogenesis and progression. Methods HL-1 rodent cardiomyocytes were infected with T. cruzi trypomastigotes of the Colombian, Y, or Tulahuen strain. RNA was serially isolated post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥ 2 or ≤ 0.5) highlighted over-represented biological pathways. Intracellular levels of reactive oxygen species (ROS) were compared between T. cruzi-infected and non-infected HL-1 cardiomyocytes. Results We found that oxidative stress-related gene ontology terms (GO terms), ‘Hypertrophy model’, ‘Apoptosis’, and ‘MAPK signaling’ pathways (all with P < 0.01) were upregulated. ‘Glutathione and one-carbon metabolism’ pathway, and ‘Cellular nitrogen compound metabolic process’ GO term (all with P < 0.001) were upregulated exclusively in the cardiomyocytes infected with the Colombian/Y strains. Mean intracellular levels of ROS were significantly higher in the T. cruzi-infected cardiomyocytes compared to the non-infected (P < 0.0001). Conclusions The upregulation of oxidative stress-related and hypertrophic pathways constitutes the universal hallmarks of the cardiomyocyte response elicited by T. cruzi infection. Nitrogen metabolism upregulation and glutathione metabolism imbalance may implicate a relationship between nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of Chagas cardiomyopathy. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Tropical Medicine and Health 51 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Trypanosoma cruzi Chagas disease Transcriptome HL-1 In vitro modeling Dilated cardiomyopathy Arctic medicine. Tropical medicine RC955-962 |
spellingShingle |
Trypanosoma cruzi Chagas disease Transcriptome HL-1 In vitro modeling Dilated cardiomyopathy Arctic medicine. Tropical medicine RC955-962 Katherine-Sofia Candray-Medina Yu Nakagama Masamichi Ito Shun Nakagama Evariste Tshibangu-Kabamba Norihiko Takeda Yuki Sugiura Yuko Nitahara Yu Michimuko-Nagahara Natsuko Kaku Yoko Onizuka Carmen-Elena Arias Maricela Mejia Karla Alas Susana Peña Yasuhiro Maejima Issei Komuro Junko Nakajima-Shimada Yasutoshi Kido Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
topic_facet |
Trypanosoma cruzi Chagas disease Transcriptome HL-1 In vitro modeling Dilated cardiomyopathy Arctic medicine. Tropical medicine RC955-962 |
description |
Abstract Background Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (CCM) progression. Our objective was to elucidate the differential transcriptomic signatures of cardiomyocytes resulting from infection with genetically discrete T. cruzi strains and explore their relationships with CCM pathogenesis and progression. Methods HL-1 rodent cardiomyocytes were infected with T. cruzi trypomastigotes of the Colombian, Y, or Tulahuen strain. RNA was serially isolated post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥ 2 or ≤ 0.5) highlighted over-represented biological pathways. Intracellular levels of reactive oxygen species (ROS) were compared between T. cruzi-infected and non-infected HL-1 cardiomyocytes. Results We found that oxidative stress-related gene ontology terms (GO terms), ‘Hypertrophy model’, ‘Apoptosis’, and ‘MAPK signaling’ pathways (all with P < 0.01) were upregulated. ‘Glutathione and one-carbon metabolism’ pathway, and ‘Cellular nitrogen compound metabolic process’ GO term (all with P < 0.001) were upregulated exclusively in the cardiomyocytes infected with the Colombian/Y strains. Mean intracellular levels of ROS were significantly higher in the T. cruzi-infected cardiomyocytes compared to the non-infected (P < 0.0001). Conclusions The upregulation of oxidative stress-related and hypertrophic pathways constitutes the universal hallmarks of the cardiomyocyte response elicited by T. cruzi infection. Nitrogen metabolism upregulation and glutathione metabolism imbalance may implicate a relationship between nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of Chagas cardiomyopathy. |
format |
Article in Journal/Newspaper |
author |
Katherine-Sofia Candray-Medina Yu Nakagama Masamichi Ito Shun Nakagama Evariste Tshibangu-Kabamba Norihiko Takeda Yuki Sugiura Yuko Nitahara Yu Michimuko-Nagahara Natsuko Kaku Yoko Onizuka Carmen-Elena Arias Maricela Mejia Karla Alas Susana Peña Yasuhiro Maejima Issei Komuro Junko Nakajima-Shimada Yasutoshi Kido |
author_facet |
Katherine-Sofia Candray-Medina Yu Nakagama Masamichi Ito Shun Nakagama Evariste Tshibangu-Kabamba Norihiko Takeda Yuki Sugiura Yuko Nitahara Yu Michimuko-Nagahara Natsuko Kaku Yoko Onizuka Carmen-Elena Arias Maricela Mejia Karla Alas Susana Peña Yasuhiro Maejima Issei Komuro Junko Nakajima-Shimada Yasutoshi Kido |
author_sort |
Katherine-Sofia Candray-Medina |
title |
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
title_short |
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
title_full |
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
title_fullStr |
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
title_full_unstemmed |
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
title_sort |
differential cardiomyocyte transcriptomic remodeling during in vitro trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses |
publisher |
BMC |
publishDate |
2023 |
url |
https://doi.org/10.1186/s41182-023-00552-6 https://doaj.org/article/3e5f69651e364dbbadcb1df0304f3316 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Tropical Medicine and Health, Vol 51, Iss 1, Pp 1-17 (2023) |
op_relation |
https://doi.org/10.1186/s41182-023-00552-6 https://doaj.org/toc/1349-4147 doi:10.1186/s41182-023-00552-6 1349-4147 https://doaj.org/article/3e5f69651e364dbbadcb1df0304f3316 |
op_doi |
https://doi.org/10.1186/s41182-023-00552-6 |
container_title |
Tropical Medicine and Health |
container_volume |
51 |
container_issue |
1 |
_version_ |
1788059391989121024 |