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Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies
Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β(1)-adrenergic receptor autoantibodies (β(1)-AABs) decreased myocardial autophagy, but the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558518/ https://www.ncbi.nlm.nih.gov/pubmed/26313913 http://dx.doi.org/10.1038/cddis.2015.237 |
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author | Wang, L Hao, H Wang, J Wang, X Zhang, S Du, Y Lv, T Zuo, L Li, Y Liu, H |
author_facet | Wang, L Hao, H Wang, J Wang, X Zhang, S Du, Y Lv, T Zuo, L Li, Y Liu, H |
author_sort | Wang, L |
collection | PubMed |
description | Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β(1)-adrenergic receptor autoantibodies (β(1)-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively β(1)-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, β(1)-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with β(1)-AAB-positive heart dysfunction. |
format | Online Article Text |
id | pubmed-4558518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45585182015-09-11 Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies Wang, L Hao, H Wang, J Wang, X Zhang, S Du, Y Lv, T Zuo, L Li, Y Liu, H Cell Death Dis Original Article Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β(1)-adrenergic receptor autoantibodies (β(1)-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively β(1)-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, β(1)-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with β(1)-AAB-positive heart dysfunction. Nature Publishing Group 2015-08 2015-08-27 /pmc/articles/PMC4558518/ /pubmed/26313913 http://dx.doi.org/10.1038/cddis.2015.237 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Wang, L Hao, H Wang, J Wang, X Zhang, S Du, Y Lv, T Zuo, L Li, Y Liu, H Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title | Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title_full | Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title_fullStr | Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title_full_unstemmed | Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title_short | Decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
title_sort | decreased autophagy: a major factor for cardiomyocyte death induced by β(1)-adrenoceptor autoantibodies |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558518/ https://www.ncbi.nlm.nih.gov/pubmed/26313913 http://dx.doi.org/10.1038/cddis.2015.237 |
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