Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction

Detalhes bibliográficos
Autor(a) principal: Inácio, José M.
Data de Publicação: 2023
Outros Autores: Cristo, Fernando, Pinheiro, Miguel, Vasques-Nóvoa, Francisco, Saraiva, Francisca, Nunes, Mafalda M., Rosas, Graça, Reis, Andreia, Coimbra, Rita, Oliveira, José Luís, Moura, Gabriela, Leite-Moreira, Adelino, Belo, José António
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/157766
Resumo: Funding Information: This work was supported by the Fundação para a Ciência e a Tecnologia (NETDIAMOND-SAICTPAC/0047/2015), Scientific Employment Stimulus to J.M.I. (Norma Transitória 8189/2018), post-doctoral fellowship to F.C. (DAI/2019/08/SAICTPAC/0047/2015), iNOVA4Health-UID/Multi/04462/2020 and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Genome Medicine Lab is funded by FCT and COMPETE2020 (iBiMED: UID/BIM/04501/2020; GenomePT: POCI-01-0145-FEDER-022184). Within the scope of the Cardiovascular R&D Center, this work was financed by national funds through FCT (UIDB/00051/2020 and UIDP/00051/2020) and RISE (LA/P/0053/2020). Publisher Copyright: © 2023 by the authors.
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spelling Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fractionheart failureHFpEFintercellular communicationmiRNA signature in HFpEFmiRNA–mRNAMedicine (miscellaneous)Biochemistry, Genetics and Molecular Biology(all)Funding Information: This work was supported by the Fundação para a Ciência e a Tecnologia (NETDIAMOND-SAICTPAC/0047/2015), Scientific Employment Stimulus to J.M.I. (Norma Transitória 8189/2018), post-doctoral fellowship to F.C. (DAI/2019/08/SAICTPAC/0047/2015), iNOVA4Health-UID/Multi/04462/2020 and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Genome Medicine Lab is funded by FCT and COMPETE2020 (iBiMED: UID/BIM/04501/2020; GenomePT: POCI-01-0145-FEDER-022184). Within the scope of the Cardiovascular R&D Center, this work was financed by national funds through FCT (UIDB/00051/2020 and UIDP/00051/2020) and RISE (LA/P/0053/2020). Publisher Copyright: © 2023 by the authors.Heart failure with preserved ejection fraction (HFpEF) represents a global health challenge, with limited therapies proven to enhance patient outcomes. This makes the elucidation of disease mechanisms and the identification of novel potential therapeutic targets a priority. Here, we performed RNA sequencing on ventricular myocardial biopsies from patients with HFpEF, prospecting to discover distinctive transcriptomic signatures. A total of 306 differentially expressed mRNAs (DEG) and 152 differentially expressed microRNAs (DEM) were identified and enriched in several biological processes involved in HF. Moreover, by integrating mRNA and microRNA expression data, we identified five potentially novel miRNA–mRNA relationships in HFpEF: the upregulated hsa-miR-25-3p, hsa-miR-26a-5p, and has-miR4429, targeting HAPLN1; and NPPB mRNA, targeted by hsa-miR-26a-5p and miR-140-3p. Exploring the predicted miRNA–mRNA interactions experimentally, we demonstrated that overexpression of the distinct miRNAs leads to the downregulation of their target genes. Interestingly, we also observed that microRNA signatures display a higher discriminative power to distinguish HFpEF sub-groups over mRNA signatures. Our results offer new mechanistic clues, which can potentially translate into new HFpEF therapies.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSRUNInácio, José M.Cristo, FernandoPinheiro, MiguelVasques-Nóvoa, FranciscoSaraiva, FranciscaNunes, Mafalda M.Rosas, GraçaReis, AndreiaCoimbra, RitaOliveira, José LuísMoura, GabrielaLeite-Moreira, AdelinoBelo, José António2023-09-13T22:18:33Z2023-082023-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/157766eng2227-9059PURE: 71089094https://doi.org/10.3390/biomedicines11082131info: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:RCAAP2024-03-11T05:40:04Zoai:run.unl.pt:10362/157766Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:56:51.895611Repositório 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 Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
title Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
spellingShingle Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
Inácio, José M.
heart failure
HFpEF
intercellular communication
miRNA signature in HFpEF
miRNA–mRNA
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
title_short Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
title_full Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
title_fullStr Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
title_full_unstemmed Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
title_sort Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
author Inácio, José M.
author_facet Inácio, José M.
Cristo, Fernando
Pinheiro, Miguel
Vasques-Nóvoa, Francisco
Saraiva, Francisca
Nunes, Mafalda M.
Rosas, Graça
Reis, Andreia
Coimbra, Rita
Oliveira, José Luís
Moura, Gabriela
Leite-Moreira, Adelino
Belo, José António
author_role author
author2 Cristo, Fernando
Pinheiro, Miguel
Vasques-Nóvoa, Francisco
Saraiva, Francisca
Nunes, Mafalda M.
Rosas, Graça
Reis, Andreia
Coimbra, Rita
Oliveira, José Luís
Moura, Gabriela
Leite-Moreira, Adelino
Belo, José António
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
iNOVA4Health - pólo NMS
RUN
dc.contributor.author.fl_str_mv Inácio, José M.
Cristo, Fernando
Pinheiro, Miguel
Vasques-Nóvoa, Francisco
Saraiva, Francisca
Nunes, Mafalda M.
Rosas, Graça
Reis, Andreia
Coimbra, Rita
Oliveira, José Luís
Moura, Gabriela
Leite-Moreira, Adelino
Belo, José António
dc.subject.por.fl_str_mv heart failure
HFpEF
intercellular communication
miRNA signature in HFpEF
miRNA–mRNA
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
topic heart failure
HFpEF
intercellular communication
miRNA signature in HFpEF
miRNA–mRNA
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
description Funding Information: This work was supported by the Fundação para a Ciência e a Tecnologia (NETDIAMOND-SAICTPAC/0047/2015), Scientific Employment Stimulus to J.M.I. (Norma Transitória 8189/2018), post-doctoral fellowship to F.C. (DAI/2019/08/SAICTPAC/0047/2015), iNOVA4Health-UID/Multi/04462/2020 and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Genome Medicine Lab is funded by FCT and COMPETE2020 (iBiMED: UID/BIM/04501/2020; GenomePT: POCI-01-0145-FEDER-022184). Within the scope of the Cardiovascular R&D Center, this work was financed by national funds through FCT (UIDB/00051/2020 and UIDP/00051/2020) and RISE (LA/P/0053/2020). Publisher Copyright: © 2023 by the authors.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-13T22:18:33Z
2023-08
2023-08-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/157766
url http://hdl.handle.net/10362/157766
dc.language.iso.fl_str_mv eng
language eng
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PURE: 71089094
https://doi.org/10.3390/biomedicines11082131
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