Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/55186 |
Resumo: | Copyright © 2022 Ribeiro, Simões, Rocha, Vala, Pinto, Ministro, Poli, Diegues, Pina, Benadjaoud, Flamant, Tamarat, Osório, Pais, Casal, Pinto, Matthiesen, Fiuza and Constantino Rosa Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapyCardiac dysfunctionCardiac muscleCardiotoxicityGlobal longitudinal strain (GLS)MicrovasculatureRadiotherapyCopyright © 2022 Ribeiro, Simões, Rocha, Vala, Pinto, Ministro, Poli, Diegues, Pina, Benadjaoud, Flamant, Tamarat, Osório, Pais, Casal, Pinto, Matthiesen, Fiuza and Constantino Rosa Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The contribution of radiotherapy, per se, to late cardiotoxicity remains controversial. To clarify its impact on the development of early cardiac dysfunction, we developed an experimental model in which the hearts of rats were exposed, in a fractionated plan, to clinically relevant doses of ionizing radiation for oncological patients that undergo thoracic radiotherapy. Rat hearts were exposed to daily doses of 0.04, 0.3, and 1.2 Gy for 23 days, achieving cumulative doses of 0.92, 6.9, and 27.6 Gy, respectively. We demonstrate that myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of >15% from baseline) in a dose-dependent manner at 18 months. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Before GLS impairment detection, several tools (qRT-PCR, mass spectrometry, and western blot) were used to assess molecular changes in the cardiac tissue. The number/expression of several genes, proteins, and KEGG pathways, related to inflammation, fibrosis, and cardiac muscle contraction, were differently expressed in the cardiac tissue according to the cumulative dose. Subclinical cardiac dysfunction occurs in a dose-dependent manner as detected by molecular changes in cardiac tissue, a predictor of the severity of global longitudinal strain impairment. Moreover, there was no dose threshold below which no myocardial deformation impairment was detected. Our findings i) contribute to developing new markers and exploring non-invasive magnetic resonance imaging to assess cardiac tissue changes as an early predictor of cardiac dysfunction; ii) should raise red flags, since there is no dose threshold below which no myocardial deformation impairment was detected and should be considered in radiation-based imaging and -guided therapeutic cardiac procedures; and iii) highlights the need for personalized clinical approaches.This work was supported by the European Community’s Horizon 2020 Program supported the MEDIRAD—Implications of Medical Low Dose Radiation Exposure granted by the Euratom Research and Training Program 2014-2014 under agreement No. 755523. The MS work was financed by the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). ARP and ATP were supported by a fellowship (SFRH/BD/121684/2016 and SFRH/BPD/123181/2016, respectively) and IV received a fellowship for Programmatic Funding (UIDP/00306/2020), all from Fundação para a Ciência e Tecnologia.FrontiersRepositório da Universidade de LisboaRibeiro, SóniaSimões, Ana RitaRocha, FilipeVala, Inês SofiaPinto, Ana TeresaMinistro, AugustoPoli, Maria EsmeraldaDiegues, Isabel MariaPina, Maria FilomenaBenadjaoud, Mohamed AmineFlamant, StephaneTamarat, RadiaOsório, HugoPais, DiogoCasal, DiogoPinto, Fausto J.Matthiesen, RuneFiuza, ManuelaSantos, Susana Constantino Rosa2022-11-22T11:57:08Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55186engFront Oncol . 2022 Jul 26;12:94552110.3389/fonc.2022.9455212234-943Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:01:47Zoai:repositorio.ul.pt:10451/55186Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:45.784541Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| title |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| spellingShingle |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy Ribeiro, Sónia Cardiac dysfunction Cardiac muscle Cardiotoxicity Global longitudinal strain (GLS) Microvasculature Radiotherapy |
| title_short |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| title_full |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| title_fullStr |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| title_full_unstemmed |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| title_sort |
Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy |
| author |
Ribeiro, Sónia |
| author_facet |
Ribeiro, Sónia Simões, Ana Rita Rocha, Filipe Vala, Inês Sofia Pinto, Ana Teresa Ministro, Augusto Poli, Maria Esmeralda Diegues, Isabel Maria Pina, Maria Filomena Benadjaoud, Mohamed Amine Flamant, Stephane Tamarat, Radia Osório, Hugo Pais, Diogo Casal, Diogo Pinto, Fausto J. Matthiesen, Rune Fiuza, Manuela Santos, Susana Constantino Rosa |
| author_role |
author |
| author2 |
Simões, Ana Rita Rocha, Filipe Vala, Inês Sofia Pinto, Ana Teresa Ministro, Augusto Poli, Maria Esmeralda Diegues, Isabel Maria Pina, Maria Filomena Benadjaoud, Mohamed Amine Flamant, Stephane Tamarat, Radia Osório, Hugo Pais, Diogo Casal, Diogo Pinto, Fausto J. Matthiesen, Rune Fiuza, Manuela Santos, Susana Constantino Rosa |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Ribeiro, Sónia Simões, Ana Rita Rocha, Filipe Vala, Inês Sofia Pinto, Ana Teresa Ministro, Augusto Poli, Maria Esmeralda Diegues, Isabel Maria Pina, Maria Filomena Benadjaoud, Mohamed Amine Flamant, Stephane Tamarat, Radia Osório, Hugo Pais, Diogo Casal, Diogo Pinto, Fausto J. Matthiesen, Rune Fiuza, Manuela Santos, Susana Constantino Rosa |
| dc.subject.por.fl_str_mv |
Cardiac dysfunction Cardiac muscle Cardiotoxicity Global longitudinal strain (GLS) Microvasculature Radiotherapy |
| topic |
Cardiac dysfunction Cardiac muscle Cardiotoxicity Global longitudinal strain (GLS) Microvasculature Radiotherapy |
| description |
Copyright © 2022 Ribeiro, Simões, Rocha, Vala, Pinto, Ministro, Poli, Diegues, Pina, Benadjaoud, Flamant, Tamarat, Osório, Pais, Casal, Pinto, Matthiesen, Fiuza and Constantino Rosa Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-11-22T11:57:08Z 2022 2022-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/55186 |
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http://hdl.handle.net/10451/55186 |
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eng |
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eng |
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Front Oncol . 2022 Jul 26;12:945521 10.3389/fonc.2022.945521 2234-943X |
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Frontiers |
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Frontiers |
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