Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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
_version_ 1783411740403302400
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
work_keys_str_mv AT gaofeng therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT kataokamasaharu therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT liuning therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT liangtian therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT huangzhanpeng therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT gufei therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT dingjian therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT liujianming therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT zhangfeng therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT maqing therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT wangyingchao therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT zhangmingming therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT huxiaoyun therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT kyselovicjan therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT huxinyang therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT puwilliamt therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT wangjianan therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT chenjinghai therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction
AT wangdazhi therapeuticroleofmir19a19bincardiacregenerationandprotectionfrommyocardialinfarction