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Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice

Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks....

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Autores principales: Wu, Xiaoyue, Liu, Xuejing, Wang, Huan, Zhou, Zihao, Yang, Chengzhi, Li, Zijian, Zhang, Youyi, Shi, XiaoLu, Zhang, Ling, Wang, Yuhui, Xian, Xunde, Liu, George, Huang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990891/
https://www.ncbi.nlm.nih.gov/pubmed/33778025
http://dx.doi.org/10.3389/fcvm.2021.644128
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author Wu, Xiaoyue
Liu, Xuejing
Wang, Huan
Zhou, Zihao
Yang, Chengzhi
Li, Zijian
Zhang, Youyi
Shi, XiaoLu
Zhang, Ling
Wang, Yuhui
Xian, Xunde
Liu, George
Huang, Wei
author_facet Wu, Xiaoyue
Liu, Xuejing
Wang, Huan
Zhou, Zihao
Yang, Chengzhi
Li, Zijian
Zhang, Youyi
Shi, XiaoLu
Zhang, Ling
Wang, Yuhui
Xian, Xunde
Liu, George
Huang, Wei
author_sort Wu, Xiaoyue
collection PubMed
description Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca(2+) current decay and an increased SR Ca(2+) content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis.
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spelling pubmed-79908912021-03-26 Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice Wu, Xiaoyue Liu, Xuejing Wang, Huan Zhou, Zihao Yang, Chengzhi Li, Zijian Zhang, Youyi Shi, XiaoLu Zhang, Ling Wang, Yuhui Xian, Xunde Liu, George Huang, Wei Front Cardiovasc Med Cardiovascular Medicine Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca(2+) current decay and an increased SR Ca(2+) content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis. Frontiers Media S.A. 2021-03-11 /pmc/articles/PMC7990891/ /pubmed/33778025 http://dx.doi.org/10.3389/fcvm.2021.644128 Text en Copyright © 2021 Wu, Liu, Wang, Zhou, Yang, Li, Zhang, Shi, Zhang, Wang, Xian, Liu and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Wu, Xiaoyue
Liu, Xuejing
Wang, Huan
Zhou, Zihao
Yang, Chengzhi
Li, Zijian
Zhang, Youyi
Shi, XiaoLu
Zhang, Ling
Wang, Yuhui
Xian, Xunde
Liu, George
Huang, Wei
Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title_full Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title_fullStr Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title_full_unstemmed Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title_short Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
title_sort seipin deficiency accelerates heart failure due to calcium handling abnormalities and endoplasmic reticulum stress in mice
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990891/
https://www.ncbi.nlm.nih.gov/pubmed/33778025
http://dx.doi.org/10.3389/fcvm.2021.644128
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