TY - JOUR
T1 - Metformin accelerates zebrafish heart regeneration by inducing autophagy
AU - Xie, Fangjing
AU - Xu, Shisan
AU - Lu, Yingying
AU - Wong, Kin Fung
AU - Sun, Lei
AU - Hasan, Kazi Md Mahmudul
AU - Ma, Alvin C.H.
AU - Tse, Gary
AU - Manno, Sinai H.C.
AU - Tian, Li
AU - Yue, Jianbo
AU - Cheng, Shuk Han
N1 - Funding Information:
We would like to thank Prof. Jeff Bronstein (University of California, Los Angeles) and Prof. Jingwei Xiong (Peking University) for kindly providing us with the Tg(cmv:GFP-LC3) and Tg(tcf21:DsRed2) lines of fish, respectively. We would like to thank Dr. Sarah E Webb (The Hong Kong University of Science and Technology) for editing the manuscript. We would also like to thank the University Research Facility in Life Sciences of The Hong Kong Polytechnic University for letting us use their FUJIFILM VisualSonics Vevo LAZR Multimodality imaging platform for this project. This work was supported by CityU Project (9610348) to S.H.C., and Hong Kong Research Grant Council (RGC) grants (11101717 and 11103620) and NSFC (21778045 and 32070702) to J.Y.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85116795001&partnerID=8YFLogxK
U2 - 10.1038/s41536-021-00172-w
DO - 10.1038/s41536-021-00172-w
M3 - Journal article
AN - SCOPUS:85116795001
VL - 6
JO - npj Regenerative Medicine
JF - npj Regenerative Medicine
SN - 2057-3995
IS - 1
M1 - 62
ER -
