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Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction

MicroRNAs are involved in the regulation of various cellular processes, including cell apoptosis and autophagy. Expression of microRNA-99a (miR-99a) is reduced in apoptotic neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia. We hypothesize that miR-99a might restore cardiac function aft...

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Autores principales: Li, Qiaoling, Xie, Jun, Li, Ruotian, Shi, Jian, Sun, Jiayin, Gu, Rong, Ding, Liang, Wang, Lian, Xu, Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119397/
https://www.ncbi.nlm.nih.gov/pubmed/24628978
http://dx.doi.org/10.1111/jcmm.12242
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author Li, Qiaoling
Xie, Jun
Li, Ruotian
Shi, Jian
Sun, Jiayin
Gu, Rong
Ding, Liang
Wang, Lian
Xu, Biao
author_facet Li, Qiaoling
Xie, Jun
Li, Ruotian
Shi, Jian
Sun, Jiayin
Gu, Rong
Ding, Liang
Wang, Lian
Xu, Biao
author_sort Li, Qiaoling
collection PubMed
description MicroRNAs are involved in the regulation of various cellular processes, including cell apoptosis and autophagy. Expression of microRNA-99a (miR-99a) is reduced in apoptotic neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia. We hypothesize that miR-99a might restore cardiac function after myocardial infarction (MI) by up-regulation of myocyte autophagy and apoptosis. We observed down-regulated miR-99a expression in NMVMs exposed to hypoxia using TaqMan quantitative reverse transcriptase-polymerase chain reaction analysis (RT-PCR). We also observed that miR-99a overexpression decreased hypoxia-mediated apoptosis in cultured NMVMs. To investigate whether overexpression of miR-99a in vivo could improve cardiac function in ischaemic heart, adult C57/BL6 mice undergoing MI were randomized into two groups and were intra-myocardially injected with lenti-99a-green fluorescent protein (GFP) or lenti-GFP (control). Four weeks after MI, lenti-99a-GFP group showed significant improvement in both left ventricular (LV) function and survival ratio, as compared to the lenti-GFP group. Histological analysis, western blotting analysis and electron microscopy revealed decreased cellular apoptosis and increased autophagy in cardiomyocytes of lenti-99a-GFP group. Furthermore, western blotting analysis showed inhibited mammalian target of rapamycin (mTOR) expression in the border zones of hearts in miR-99a-treated group. Our results demonstrate that miR-99a overexpression improves both cardiac function and survival ratio in a murine model of MI by preventing cell apoptosis and increasing autophagy via an mTOR/P70/S6K signalling pathway. These findings suggest that miR-99a plays a cardioprotective role in post-infarction LV remodelling and increased expression of miR-99a may have a therapeutic potential in ischaemic heart disease.
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spelling pubmed-41193972014-12-03 Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction Li, Qiaoling Xie, Jun Li, Ruotian Shi, Jian Sun, Jiayin Gu, Rong Ding, Liang Wang, Lian Xu, Biao J Cell Mol Med Original Articles MicroRNAs are involved in the regulation of various cellular processes, including cell apoptosis and autophagy. Expression of microRNA-99a (miR-99a) is reduced in apoptotic neonatal mice ventricular myocytes (NMVMs) subjected to hypoxia. We hypothesize that miR-99a might restore cardiac function after myocardial infarction (MI) by up-regulation of myocyte autophagy and apoptosis. We observed down-regulated miR-99a expression in NMVMs exposed to hypoxia using TaqMan quantitative reverse transcriptase-polymerase chain reaction analysis (RT-PCR). We also observed that miR-99a overexpression decreased hypoxia-mediated apoptosis in cultured NMVMs. To investigate whether overexpression of miR-99a in vivo could improve cardiac function in ischaemic heart, adult C57/BL6 mice undergoing MI were randomized into two groups and were intra-myocardially injected with lenti-99a-green fluorescent protein (GFP) or lenti-GFP (control). Four weeks after MI, lenti-99a-GFP group showed significant improvement in both left ventricular (LV) function and survival ratio, as compared to the lenti-GFP group. Histological analysis, western blotting analysis and electron microscopy revealed decreased cellular apoptosis and increased autophagy in cardiomyocytes of lenti-99a-GFP group. Furthermore, western blotting analysis showed inhibited mammalian target of rapamycin (mTOR) expression in the border zones of hearts in miR-99a-treated group. Our results demonstrate that miR-99a overexpression improves both cardiac function and survival ratio in a murine model of MI by preventing cell apoptosis and increasing autophagy via an mTOR/P70/S6K signalling pathway. These findings suggest that miR-99a plays a cardioprotective role in post-infarction LV remodelling and increased expression of miR-99a may have a therapeutic potential in ischaemic heart disease. BlackWell Publishing Ltd 2014-05 2014-03-13 /pmc/articles/PMC4119397/ /pubmed/24628978 http://dx.doi.org/10.1111/jcmm.12242 Text en © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Qiaoling
Xie, Jun
Li, Ruotian
Shi, Jian
Sun, Jiayin
Gu, Rong
Ding, Liang
Wang, Lian
Xu, Biao
Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title_full Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title_fullStr Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title_full_unstemmed Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title_short Overexpression of microRNA-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
title_sort overexpression of microrna-99a attenuates heart remodelling and improves cardiac performance after myocardial infarction
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119397/
https://www.ncbi.nlm.nih.gov/pubmed/24628978
http://dx.doi.org/10.1111/jcmm.12242
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