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Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits

Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Ca...

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Autores principales: Ichikawa, Yasuhiro, Zemljic-Harpf, Alice E., Zhang, Zheng, McKirnan, M. Dan, Manso, Ana Maria, Ross, Robert S., Hammond, H. Kirk, Patel, Hemal H., Roth, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428970/
https://www.ncbi.nlm.nih.gov/pubmed/28498861
http://dx.doi.org/10.1371/journal.pone.0177660
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author Ichikawa, Yasuhiro
Zemljic-Harpf, Alice E.
Zhang, Zheng
McKirnan, M. Dan
Manso, Ana Maria
Ross, Robert S.
Hammond, H. Kirk
Patel, Hemal H.
Roth, David M.
author_facet Ichikawa, Yasuhiro
Zemljic-Harpf, Alice E.
Zhang, Zheng
McKirnan, M. Dan
Manso, Ana Maria
Ross, Robert S.
Hammond, H. Kirk
Patel, Hemal H.
Roth, David M.
author_sort Ichikawa, Yasuhiro
collection PubMed
description Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and related membrane repair proteins can function as cardioprotective proteins. Expression of these proteins in anthracycline-induced heart failure has not been evaluated. We tested the hypothesis that daunorubicin alters cardioprotective protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg, IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of daunorubicin resulted in progressive reduced left ventricular function. Cav-3 expression in the heart was unchanged at three weeks of daunorubicin and increased in nine week treated rabbits when compared to control hearts. Electron microscopy showed caveolae in the heart were increased and mitochondrial number and size were decreased after nine weeks of daunorubicin. Activated beta-1 (β1) integrin and the membrane repair protein MG53 were increased after nine weeks of daunorubicin vs. controls with no change at the three week time point. The results suggest a potential pathophysiological role for Cav3, integrins and membrane repair in daunorubicin-induced heart failure.
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spelling pubmed-54289702017-05-26 Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits Ichikawa, Yasuhiro Zemljic-Harpf, Alice E. Zhang, Zheng McKirnan, M. Dan Manso, Ana Maria Ross, Robert S. Hammond, H. Kirk Patel, Hemal H. Roth, David M. PLoS One Research Article Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and related membrane repair proteins can function as cardioprotective proteins. Expression of these proteins in anthracycline-induced heart failure has not been evaluated. We tested the hypothesis that daunorubicin alters cardioprotective protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg, IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of daunorubicin resulted in progressive reduced left ventricular function. Cav-3 expression in the heart was unchanged at three weeks of daunorubicin and increased in nine week treated rabbits when compared to control hearts. Electron microscopy showed caveolae in the heart were increased and mitochondrial number and size were decreased after nine weeks of daunorubicin. Activated beta-1 (β1) integrin and the membrane repair protein MG53 were increased after nine weeks of daunorubicin vs. controls with no change at the three week time point. The results suggest a potential pathophysiological role for Cav3, integrins and membrane repair in daunorubicin-induced heart failure. Public Library of Science 2017-05-12 /pmc/articles/PMC5428970/ /pubmed/28498861 http://dx.doi.org/10.1371/journal.pone.0177660 Text en © 2017 Ichikawa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ichikawa, Yasuhiro
Zemljic-Harpf, Alice E.
Zhang, Zheng
McKirnan, M. Dan
Manso, Ana Maria
Ross, Robert S.
Hammond, H. Kirk
Patel, Hemal H.
Roth, David M.
Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title_full Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title_fullStr Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title_full_unstemmed Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title_short Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
title_sort modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428970/
https://www.ncbi.nlm.nih.gov/pubmed/28498861
http://dx.doi.org/10.1371/journal.pone.0177660
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