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Metformin accelerates zebrafish heart regeneration by inducing autophagy

Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans...

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Autores principales: Xie, Fangjing, Xu, Shisan, Lu, Yingying, Wong, Kin Fung, Sun, Lei, Hasan, Kazi Md Mahmudul, Ma, Alvin C. H., Tse, Gary, Manno, Sinai H. C., Tian, Li, Yue, Jianbo, Cheng, Shuk Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501080/
https://www.ncbi.nlm.nih.gov/pubmed/34625572
http://dx.doi.org/10.1038/s41536-021-00172-w
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author Xie, Fangjing
Xu, Shisan
Lu, Yingying
Wong, Kin Fung
Sun, Lei
Hasan, Kazi Md Mahmudul
Ma, Alvin C. H.
Tse, Gary
Manno, Sinai H. C.
Tian, Li
Yue, Jianbo
Cheng, Shuk Han
author_facet Xie, Fangjing
Xu, Shisan
Lu, Yingying
Wong, Kin Fung
Sun, Lei
Hasan, Kazi Md Mahmudul
Ma, Alvin C. H.
Tse, Gary
Manno, Sinai H. C.
Tian, Li
Yue, Jianbo
Cheng, Shuk Han
author_sort Xie, Fangjing
collection PubMed
description Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction.
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spelling pubmed-85010802021-10-22 Metformin accelerates zebrafish heart regeneration by inducing autophagy Xie, Fangjing Xu, Shisan Lu, Yingying Wong, Kin Fung Sun, Lei Hasan, Kazi Md Mahmudul Ma, Alvin C. H. Tse, Gary Manno, Sinai H. C. Tian, Li Yue, Jianbo Cheng, Shuk Han NPJ Regen Med Article Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction. Nature Publishing Group UK 2021-10-08 /pmc/articles/PMC8501080/ /pubmed/34625572 http://dx.doi.org/10.1038/s41536-021-00172-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xie, Fangjing
Xu, Shisan
Lu, Yingying
Wong, Kin Fung
Sun, Lei
Hasan, Kazi Md Mahmudul
Ma, Alvin C. H.
Tse, Gary
Manno, Sinai H. C.
Tian, Li
Yue, Jianbo
Cheng, Shuk Han
Metformin accelerates zebrafish heart regeneration by inducing autophagy
title Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_full Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_fullStr Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_full_unstemmed Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_short Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_sort metformin accelerates zebrafish heart regeneration by inducing autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501080/
https://www.ncbi.nlm.nih.gov/pubmed/34625572
http://dx.doi.org/10.1038/s41536-021-00172-w
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