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Molecular Changes In Cardiac Tissue As A New Marker To Predict Cardiac Dysfunction Induced By Radiotherapy

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...

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Autores principales: Ribeiro, Sónia, Simões, Ana Rita, Rocha, Filipe, Vala, Inês Sofia, Pinto, Ana Teresa, Ministro, Augusto, Poli, Esmeralda, Diegues, Isabel Maria, Pina, Filomena, Benadjaoud, Mohamed Amine, Flamant, Stephane, Tamarat, Radia, Osório, Hugo, Pais, Diogo, Casal, Diogo, Pinto, Fausto José, Matthiesen, Rune, Fiuza, Manuela, Constantino Rosa Santos, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360508/
https://www.ncbi.nlm.nih.gov/pubmed/35957913
http://dx.doi.org/10.3389/fonc.2022.945521
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author Ribeiro, Sónia
Simões, Ana Rita
Rocha, Filipe
Vala, Inês Sofia
Pinto, Ana Teresa
Ministro, Augusto
Poli, Esmeralda
Diegues, Isabel Maria
Pina, Filomena
Benadjaoud, Mohamed Amine
Flamant, Stephane
Tamarat, Radia
Osório, Hugo
Pais, Diogo
Casal, Diogo
Pinto, Fausto José
Matthiesen, Rune
Fiuza, Manuela
Constantino Rosa Santos, Susana
author_facet Ribeiro, Sónia
Simões, Ana Rita
Rocha, Filipe
Vala, Inês Sofia
Pinto, Ana Teresa
Ministro, Augusto
Poli, Esmeralda
Diegues, Isabel Maria
Pina, Filomena
Benadjaoud, Mohamed Amine
Flamant, Stephane
Tamarat, Radia
Osório, Hugo
Pais, Diogo
Casal, Diogo
Pinto, Fausto José
Matthiesen, Rune
Fiuza, Manuela
Constantino Rosa Santos, Susana
author_sort Ribeiro, Sónia
collection PubMed
description 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.
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spelling pubmed-93605082022-08-10 Molecular Changes In Cardiac Tissue As A New Marker To Predict Cardiac Dysfunction Induced By Radiotherapy Ribeiro, Sónia Simões, Ana Rita Rocha, Filipe Vala, Inês Sofia Pinto, Ana Teresa Ministro, Augusto Poli, Esmeralda Diegues, Isabel Maria Pina, Filomena Benadjaoud, Mohamed Amine Flamant, Stephane Tamarat, Radia Osório, Hugo Pais, Diogo Casal, Diogo Pinto, Fausto José Matthiesen, Rune Fiuza, Manuela Constantino Rosa Santos, Susana Front Oncol Oncology 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. Frontiers Media S.A. 2022-07-26 /pmc/articles/PMC9360508/ /pubmed/35957913 http://dx.doi.org/10.3389/fonc.2022.945521 Text en Copyright © 2022 Ribeiro, Simões, Rocha, Vala, Pinto, Ministro, Poli, Diegues, Pina, Benadjaoud, Flamant, Tamarat, Osório, Pais, Casal, Pinto, Matthiesen, Fiuza and Constantino Rosa Santos https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Oncology
Ribeiro, Sónia
Simões, Ana Rita
Rocha, Filipe
Vala, Inês Sofia
Pinto, Ana Teresa
Ministro, Augusto
Poli, Esmeralda
Diegues, Isabel Maria
Pina, Filomena
Benadjaoud, Mohamed Amine
Flamant, Stephane
Tamarat, Radia
Osório, Hugo
Pais, Diogo
Casal, Diogo
Pinto, Fausto José
Matthiesen, Rune
Fiuza, Manuela
Constantino Rosa Santos, Susana
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
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_short 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
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360508/
https://www.ncbi.nlm.nih.gov/pubmed/35957913
http://dx.doi.org/10.3389/fonc.2022.945521
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