The role of FGF21 in inhibition of heart failure with empagliflozin and related mechanisms
10.16438/j.0513-4870.2021-1753
- VernacularTitle:FGF21在依帕列净抑制心衰中的作用和机制研究
- Author:
Meng-xue ZHANG
1
;
Yuan-yu WANG
2
;
Ya-jun DUAN
3
;
Shuang ZHANG
1
Author Information
1. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China
2. Beijing Institute of Biomedicine, Beijing 100091, China
3. The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei 230022, China
- Publication Type:Research Article
- Keywords:
empagliflozin;
fibroblast growth factor 21;
heart failure;
oxorubicin;
fibrosis;
inflammation;
oxidative stress
- From:
Acta Pharmaceutica Sinica
2022;57(6):1664-1672
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to investigate the role of fibroblast growth factor 21 (FGF21) in empagliflozin (EMP) in treatment of heart failure and the related mechanisms. FGF21 knockout (FGF21 KO) and littermate wild-type (WT) mice induced by doxorubicin (Dox) were used to establish heart failure mouse model in vivo. The experiment process and animal welfare follow the regulations of Animal Ethics Committee of Hefei University of Technology strictly. The results suggest that Dox (5 mg·kg-1) induced typical heart failure symptoms in both WT and FGF21 KO mice. In WT mice, EMP (10 mg·kg-1) significantly improved Dox-induced cardiac atrophy, decreased myocardial systolic function, decreased left ventricular ejection fraction and shortened fraction; EMP treatment also significantly inhibited the increase of Dox-induced cardiotoxicity indexes (aspartate amino transferase, creatine kinase, hydroxybutyrate dehydrogenase, lactate dehydrogenase) in mice. Dox induced cardiac fibrosis, inflammation and oxidative stress were also significantly improved by EMP. However, in FGF21 KO mice, the therapeutic effects of EMP on heart failure was significantly inhibited. The results suggest that the function of EMP in treating heart failure partly depends on the presence of FGF21, and the mechanism may be related to the effect of FGF21 on improving fibrosis, inflammation and oxidative stress.
