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Molecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapy

2022Artigo científico Acesso aberto
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dc.contributor.authorRibeiro, Sónia
dc.contributor.authorSimões, Ana Rita
dc.contributor.authorRocha, Filipe
dc.contributor.authorVala, Inês Sofia
dc.contributor.authorPinto, Ana Teresa
dc.contributor.authorMinistro, Augusto
dc.contributor.authorPoli, Maria Esmeralda
dc.contributor.authorDiegues, Isabel Maria
dc.contributor.authorPina, Maria Filomena
dc.contributor.authorBenadjaoud, Mohamed Amine
dc.contributor.authorFlamant, Stephane
dc.contributor.authorTamarat, Radia
dc.contributor.authorOsório, Hugo
dc.contributor.authorPais, Diogo
dc.contributor.authorCasal, Diogo
dc.contributor.authorPinto, Fausto J.
dc.contributor.authorMatthiesen, Rune
dc.contributor.authorFiuza, Manuela
dc.contributor.authorSantos, Susana Constantino Rosa
dc.date.accessioned2022-11-22T11:57:08Z
dc.date.available2022-11-22T11:57:08Z
dc.date.issued2022
dc.descriptionCopyright © 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.pt_PT
dc.description.abstractThe 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.pt_PT
dc.description.sponsorshipThis 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Oncol . 2022 Jul 26;12:945521pt_PT
dc.identifier.doi10.3389/fonc.2022.945521pt_PT
dc.identifier.eissn2234-943X
dc.identifier.urihttp://hdl.handle.net/10451/55186
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relation755523pt_PT
dc.relationIDENTIFYING THE DOSES OF IONIZING RADIATION THAT INDUCE CARDIOVASCULAR TOXICITY: A STEP TO PREVENT IT
dc.relationAngiogenesis modulation in healthy tissues exposed to ionizing radiation during radiotherapy
dc.relationCardiovascular Centre at the University of Lisbon
dc.relationLISBOA-01-0145-FEDER-022125pt_PT
dc.relation.publisherversionhttps://www.frontiersin.org/journals/oncologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCardiac dysfunctionpt_PT
dc.subjectCardiac musclept_PT
dc.subjectCardiotoxicitypt_PT
dc.subjectGlobal longitudinal strain (GLS)pt_PT
dc.subjectMicrovasculaturept_PT
dc.subjectRadiotherapypt_PT
dc.titleMolecular changes in cardiac tissue as a new marker to predict cardiac dysfunction induced by radiotherapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BD/121684/2016
oaire.awardNumberSFRH/BPD/123181/2016
oaire.awardNumberUIDP/00306/2020
oaire.awardTitleIDENTIFYING THE DOSES OF IONIZING RADIATION THAT INDUCE CARDIOVASCULAR TOXICITY: A STEP TO PREVENT IT
oaire.awardTitleAngiogenesis modulation in healthy tissues exposed to ionizing radiation during radiotherapy
oaire.awardTitleCardiovascular Centre at the University of Lisbon
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F121684%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F123181%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00306%2F2020/PT
oaire.citation.titleFrontiers in Oncologypt_PT
oaire.citation.volume12pt_PT
oaire.fundingStreamOE
oaire.fundingStream6817 - DCRRNI ID
person.familyNameRIBEIRO
person.familyNameNunes Rocha
person.familyNameAlmeida Ministro
person.familyNamePoli
person.familyNamePina
person.familyNamePinto
person.familyNameFiuza
person.familyNameConstantino Rosa Santos
person.givenNameSÓNIA
person.givenNameFilipe
person.givenNameAugusto Manuel
person.givenNameMaria Esmeralda
person.givenNameMaria Filomena Brazão Carvalho De
person.givenNameFausto J.
person.givenNameManuela
person.givenNameSusana
person.identifier1308889
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person.identifier.orcid0000-0002-8034-4529
person.identifier.orcid0000-0002-7742-6195
person.identifier.orcid0000-0002-5711-1292
person.identifier.ridG-6776-2015
person.identifier.ridG-9363-2015
person.identifier.scopus-author-id7102740158
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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