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Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity
Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomizatio...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132758/ https://www.ncbi.nlm.nih.gov/pubmed/37126556 http://dx.doi.org/10.1126/sciadv.add4984 |
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author | Schmidt, Amand F. Bourfiss, Mimount Alasiri, Abdulrahman Puyol-Anton, Esther Chopade, Sandesh van Vugt, Marion van der Laan, Sander W. Gross, Christian Clarkson, Chris Henry, Albert Lumbers, Tom R. van der Harst, Pim Franceschini, Nora Bis, Joshua C. Velthuis, Birgitta K. te Riele, Anneline S. J. M. Hingorani, Aroon D. Ruijsink, Bram Asselbergs, Folkert W. van Setten, Jessica Finan, Chris |
author_facet | Schmidt, Amand F. Bourfiss, Mimount Alasiri, Abdulrahman Puyol-Anton, Esther Chopade, Sandesh van Vugt, Marion van der Laan, Sander W. Gross, Christian Clarkson, Chris Henry, Albert Lumbers, Tom R. van der Harst, Pim Franceschini, Nora Bis, Joshua C. Velthuis, Birgitta K. te Riele, Anneline S. J. M. Hingorani, Aroon D. Ruijsink, Bram Asselbergs, Folkert W. van Setten, Jessica Finan, Chris |
author_sort | Schmidt, Amand F. |
collection | PubMed |
description | Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confidence interval, 0.31 to 0.72) could be mapped to compounds with known oncological indications or side effects. These findings provide leads to facilitate drug development for cardiac disease and suggest that cardiotoxicities of several cancer treatments might represent mechanism-based adverse effects. |
format | Online Article Text |
id | pubmed-10132758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-101327582023-04-27 Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity Schmidt, Amand F. Bourfiss, Mimount Alasiri, Abdulrahman Puyol-Anton, Esther Chopade, Sandesh van Vugt, Marion van der Laan, Sander W. Gross, Christian Clarkson, Chris Henry, Albert Lumbers, Tom R. van der Harst, Pim Franceschini, Nora Bis, Joshua C. Velthuis, Birgitta K. te Riele, Anneline S. J. M. Hingorani, Aroon D. Ruijsink, Bram Asselbergs, Folkert W. van Setten, Jessica Finan, Chris Sci Adv Biomedicine and Life Sciences Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confidence interval, 0.31 to 0.72) could be mapped to compounds with known oncological indications or side effects. These findings provide leads to facilitate drug development for cardiac disease and suggest that cardiotoxicities of several cancer treatments might represent mechanism-based adverse effects. American Association for the Advancement of Science 2023-04-26 /pmc/articles/PMC10132758/ /pubmed/37126556 http://dx.doi.org/10.1126/sciadv.add4984 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Schmidt, Amand F. Bourfiss, Mimount Alasiri, Abdulrahman Puyol-Anton, Esther Chopade, Sandesh van Vugt, Marion van der Laan, Sander W. Gross, Christian Clarkson, Chris Henry, Albert Lumbers, Tom R. van der Harst, Pim Franceschini, Nora Bis, Joshua C. Velthuis, Birgitta K. te Riele, Anneline S. J. M. Hingorani, Aroon D. Ruijsink, Bram Asselbergs, Folkert W. van Setten, Jessica Finan, Chris Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title | Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title_full | Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title_fullStr | Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title_full_unstemmed | Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title_short | Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity |
title_sort | druggable proteins influencing cardiac structure and function: implications for heart failure therapies and cancer cardiotoxicity |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132758/ https://www.ncbi.nlm.nih.gov/pubmed/37126556 http://dx.doi.org/10.1126/sciadv.add4984 |
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