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The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration
The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin‐related protein‐1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided in...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533471/ https://www.ncbi.nlm.nih.gov/pubmed/30938090 http://dx.doi.org/10.1111/jcmm.14227 |
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author | Yu, Ziqing Gong, Xue Yu, Yong Li, Minghui Liang, Yixiu Qin, Shengmei Fulati, Zibire Zhou, Nianwei Shu, Xianhong Nie, Zhenning Dai, Shimo Chen, Xueying Wang, Jingfeng Chen, Ruizhen Su, Yangang Ge, Junbo |
author_facet | Yu, Ziqing Gong, Xue Yu, Yong Li, Minghui Liang, Yixiu Qin, Shengmei Fulati, Zibire Zhou, Nianwei Shu, Xianhong Nie, Zhenning Dai, Shimo Chen, Xueying Wang, Jingfeng Chen, Ruizhen Su, Yangang Ge, Junbo |
author_sort | Yu, Ziqing |
collection | PubMed |
description | The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin‐related protein‐1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8‐week rapid atrial pacing or 4‐week rapid atrial pacing and 4‐week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin‐II and angiotensin‐II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down‐regulating MCU and up‐regulating DNM1L/Drp1. Cell stretching reversed the angiotensin‐II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down‐regulated MCU, up‐regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin‐II‐induced cellular enlargement. |
format | Online Article Text |
id | pubmed-6533471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65334712019-06-01 The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration Yu, Ziqing Gong, Xue Yu, Yong Li, Minghui Liang, Yixiu Qin, Shengmei Fulati, Zibire Zhou, Nianwei Shu, Xianhong Nie, Zhenning Dai, Shimo Chen, Xueying Wang, Jingfeng Chen, Ruizhen Su, Yangang Ge, Junbo J Cell Mol Med Original Articles The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin‐related protein‐1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8‐week rapid atrial pacing or 4‐week rapid atrial pacing and 4‐week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin‐II and angiotensin‐II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down‐regulating MCU and up‐regulating DNM1L/Drp1. Cell stretching reversed the angiotensin‐II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down‐regulated MCU, up‐regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin‐II‐induced cellular enlargement. John Wiley and Sons Inc. 2019-04-02 2019-06 /pmc/articles/PMC6533471/ /pubmed/30938090 http://dx.doi.org/10.1111/jcmm.14227 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Yu, Ziqing Gong, Xue Yu, Yong Li, Minghui Liang, Yixiu Qin, Shengmei Fulati, Zibire Zhou, Nianwei Shu, Xianhong Nie, Zhenning Dai, Shimo Chen, Xueying Wang, Jingfeng Chen, Ruizhen Su, Yangang Ge, Junbo The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title | The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title_full | The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title_fullStr | The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title_full_unstemmed | The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title_short | The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
title_sort | mechanical effects of crt promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533471/ https://www.ncbi.nlm.nih.gov/pubmed/30938090 http://dx.doi.org/10.1111/jcmm.14227 |
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