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Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies

Anthracyclines, including doxorubicin, idarubicin, and epirubicin, are common antitumor drugs as well as well-known cardiotoxic agents. This study analyzed the proteomics alteration in cardiac tissues caused by these 3 anthracyclines analogs. The in vitro human cardiac microtissues were exposed to d...

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Autores principales: Nguyen, Nhan, Souza, Terezinha, Verheijen, Marcha C. T., Gmuender, Hans, Selevsek, Nathalie, Schlapbach, Ralph, Kleinjans, Jos, Jennen, Danyel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239409/
https://www.ncbi.nlm.nih.gov/pubmed/34211507
http://dx.doi.org/10.3389/fgene.2021.695625
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author Nguyen, Nhan
Souza, Terezinha
Verheijen, Marcha C. T.
Gmuender, Hans
Selevsek, Nathalie
Schlapbach, Ralph
Kleinjans, Jos
Jennen, Danyel
author_facet Nguyen, Nhan
Souza, Terezinha
Verheijen, Marcha C. T.
Gmuender, Hans
Selevsek, Nathalie
Schlapbach, Ralph
Kleinjans, Jos
Jennen, Danyel
author_sort Nguyen, Nhan
collection PubMed
description Anthracyclines, including doxorubicin, idarubicin, and epirubicin, are common antitumor drugs as well as well-known cardiotoxic agents. This study analyzed the proteomics alteration in cardiac tissues caused by these 3 anthracyclines analogs. The in vitro human cardiac microtissues were exposed to drugs in 2 weeks; the proteomic data were measured at 7 time points. The heart biopsy data were collected from heart failure patients, in which some patients underwent anthracycline treatment. The anthracyclines-affected proteins were separately identified in the in vitro and in vivo dataset using the WGCNA method. These proteins engage in different cellular pathways including translation, metabolism, mitochondrial function, muscle contraction, and signaling pathways. From proteins detected in 2 datasets, a protein-protein network was established with 4 hub proteins, and 7 weighted proteins from both cardiac microtissue and human biopsies data. These 11 proteins, which involve in mitochondrial functions and the NF-κB signaling pathway, could provide insights into the anthracycline toxic mechanism. Some of them, such as HSPA5, BAG3, and SH3BGRL, are cardiac therapy targets or cardiotoxicity biomarkers. Other proteins, such as ATP5F1B and EEF1D, showed similar responses in both the in vitro and in vivo data. This suggests that the in vitro outcomes could link to clinical phenomena in proteomic analysis.
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spelling pubmed-82394092021-06-30 Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies Nguyen, Nhan Souza, Terezinha Verheijen, Marcha C. T. Gmuender, Hans Selevsek, Nathalie Schlapbach, Ralph Kleinjans, Jos Jennen, Danyel Front Genet Genetics Anthracyclines, including doxorubicin, idarubicin, and epirubicin, are common antitumor drugs as well as well-known cardiotoxic agents. This study analyzed the proteomics alteration in cardiac tissues caused by these 3 anthracyclines analogs. The in vitro human cardiac microtissues were exposed to drugs in 2 weeks; the proteomic data were measured at 7 time points. The heart biopsy data were collected from heart failure patients, in which some patients underwent anthracycline treatment. The anthracyclines-affected proteins were separately identified in the in vitro and in vivo dataset using the WGCNA method. These proteins engage in different cellular pathways including translation, metabolism, mitochondrial function, muscle contraction, and signaling pathways. From proteins detected in 2 datasets, a protein-protein network was established with 4 hub proteins, and 7 weighted proteins from both cardiac microtissue and human biopsies data. These 11 proteins, which involve in mitochondrial functions and the NF-κB signaling pathway, could provide insights into the anthracycline toxic mechanism. Some of them, such as HSPA5, BAG3, and SH3BGRL, are cardiac therapy targets or cardiotoxicity biomarkers. Other proteins, such as ATP5F1B and EEF1D, showed similar responses in both the in vitro and in vivo data. This suggests that the in vitro outcomes could link to clinical phenomena in proteomic analysis. Frontiers Media S.A. 2021-06-15 /pmc/articles/PMC8239409/ /pubmed/34211507 http://dx.doi.org/10.3389/fgene.2021.695625 Text en Copyright © 2021 Nguyen, Souza, Verheijen, Gmuender, Selevsek, Schlapbach, Kleinjans and Jennen. 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 Genetics
Nguyen, Nhan
Souza, Terezinha
Verheijen, Marcha C. T.
Gmuender, Hans
Selevsek, Nathalie
Schlapbach, Ralph
Kleinjans, Jos
Jennen, Danyel
Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title_full Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title_fullStr Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title_full_unstemmed Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title_short Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
title_sort translational proteomics analysis of anthracycline-induced cardiotoxicity from cardiac microtissues to human heart biopsies
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239409/
https://www.ncbi.nlm.nih.gov/pubmed/34211507
http://dx.doi.org/10.3389/fgene.2021.695625
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