AUTHOR=Zhang Jie , Zuo Zhi , Li Jianxuan , Wang Ying , Huang Jia , Xu Lili , Jin Kejia , Lu Hao , Dai Yuxiang 

TITLE=In situ assessment of statins’ effect on autophagic activity in zebrafish larvae cardiomyocytes

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.921829

DOI=10.3389/fcvm.2022.921829

ISSN=2297-055X

ABSTRACT=Improving the survival rate of cardiomyocytes is the key point to treat most of heart diseases, targeting autophagy represent a potential advanced therapeutic approach. Monitoring autophagic activity in cardiomyocytes in vivo will be a useful tool for studying autophagy-related heart disease and screening autophagy-modulating drugs. Zebrafish, danio rerio, has been proved as an animal model for studying heart diseases in vivo. Take the advantage of zebrafish, especially the imaging of intact animals, here we generated two stable transgenic zebrafish lines which specifically expressed EGFP-map1lc3b or mRFP-EGFP-map1lc3b in cardiomyocytes under the promoter of myosin light chain 7. We firstly used a few of known autophagy-modulating drugs to confirm their usefulness. By quantifying the density of autophaogosomes and autolysosomes, autophagy inducer and inhibitors showed their regulatory functions which were consistent with previous studies. With the two lines, we then found a significant increase in the density of autophagosomes but not autolysosomes in zebrafish cardiomyocytes at the early developmental stages, indicating the involvement of autophagy in early heart development. To prove their applicability, we also tested five clinical statins by the two lines. And we found that statins did not change the density of autophagosomes but reduced the density of autolysosomes in cardiomyocytes, implying their regulation in autophagic flux. Our study provides novel in vivo animal models for monitoring autophagic activity in cardiomyocytes, which could be used to study the autophagy-related cardiomyopathy and drug screening.