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Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction
The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart fail...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470165/ https://www.ncbi.nlm.nih.gov/pubmed/30996254 http://dx.doi.org/10.1038/s41467-019-09530-1 |
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author | Gao, Feng Kataoka, Masaharu Liu, Ning Liang, Tian Huang, Zhan-Peng Gu, Fei Ding, Jian Liu, Jianming Zhang, Feng Ma, Qing Wang, Yingchao Zhang, Mingming Hu, Xiaoyun Kyselovic, Jan Hu, Xinyang Pu, William T. Wang, Jian’an Chen, Jinghai Wang, Da-Zhi |
author_facet | Gao, Feng Kataoka, Masaharu Liu, Ning Liang, Tian Huang, Zhan-Peng Gu, Fei Ding, Jian Liu, Jianming Zhang, Feng Ma, Qing Wang, Yingchao Zhang, Mingming Hu, Xiaoyun Kyselovic, Jan Hu, Xinyang Pu, William T. Wang, Jian’an Chen, Jinghai Wang, Da-Zhi |
author_sort | Gao, Feng |
collection | PubMed |
description | The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure. |
format | Online Article Text |
id | pubmed-6470165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64701652019-04-19 Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction Gao, Feng Kataoka, Masaharu Liu, Ning Liang, Tian Huang, Zhan-Peng Gu, Fei Ding, Jian Liu, Jianming Zhang, Feng Ma, Qing Wang, Yingchao Zhang, Mingming Hu, Xiaoyun Kyselovic, Jan Hu, Xinyang Pu, William T. Wang, Jian’an Chen, Jinghai Wang, Da-Zhi Nat Commun Article The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure. Nature Publishing Group UK 2019-04-17 /pmc/articles/PMC6470165/ /pubmed/30996254 http://dx.doi.org/10.1038/s41467-019-09530-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gao, Feng Kataoka, Masaharu Liu, Ning Liang, Tian Huang, Zhan-Peng Gu, Fei Ding, Jian Liu, Jianming Zhang, Feng Ma, Qing Wang, Yingchao Zhang, Mingming Hu, Xiaoyun Kyselovic, Jan Hu, Xinyang Pu, William T. Wang, Jian’an Chen, Jinghai Wang, Da-Zhi Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title | Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title_full | Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title_fullStr | Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title_full_unstemmed | Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title_short | Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction |
title_sort | therapeutic role of mir-19a/19b in cardiac regeneration and protection from myocardial infarction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470165/ https://www.ncbi.nlm.nih.gov/pubmed/30996254 http://dx.doi.org/10.1038/s41467-019-09530-1 |
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