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Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model
Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059907/ https://www.ncbi.nlm.nih.gov/pubmed/30062212 http://dx.doi.org/10.1016/j.jacbts.2017.12.007 |
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author | Truitt, Rachel Mu, Anbin Corbin, Elise A. Vite, Alexia Brandimarto, Jeffrey Ky, Bonnie Margulies, Kenneth B. |
author_facet | Truitt, Rachel Mu, Anbin Corbin, Elise A. Vite, Alexia Brandimarto, Jeffrey Ky, Bonnie Margulies, Kenneth B. |
author_sort | Truitt, Rachel |
collection | PubMed |
description | Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses. Simulated increases in afterload augmented sunitinib cardiotoxicity in both rat and human microtissues, which suggest that antihypertensive therapy may be a strategy to prevent left ventricular dysfunction in patients treated with sunitinib. |
format | Online Article Text |
id | pubmed-6059907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60599072018-07-30 Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model Truitt, Rachel Mu, Anbin Corbin, Elise A. Vite, Alexia Brandimarto, Jeffrey Ky, Bonnie Margulies, Kenneth B. JACC Basic Transl Sci PRECLINICAL RESEARCH Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses. Simulated increases in afterload augmented sunitinib cardiotoxicity in both rat and human microtissues, which suggest that antihypertensive therapy may be a strategy to prevent left ventricular dysfunction in patients treated with sunitinib. Elsevier 2018-05-30 /pmc/articles/PMC6059907/ /pubmed/30062212 http://dx.doi.org/10.1016/j.jacbts.2017.12.007 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | PRECLINICAL RESEARCH Truitt, Rachel Mu, Anbin Corbin, Elise A. Vite, Alexia Brandimarto, Jeffrey Ky, Bonnie Margulies, Kenneth B. Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title | Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title_full | Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title_fullStr | Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title_full_unstemmed | Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title_short | Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model |
title_sort | increased afterload augments sunitinib-induced cardiotoxicity in an engineered cardiac microtissue model |
topic | PRECLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059907/ https://www.ncbi.nlm.nih.gov/pubmed/30062212 http://dx.doi.org/10.1016/j.jacbts.2017.12.007 |
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