Dapagliflozin Mediates Plin5/PPARα Signaling Axis to Attenuate Cardiac Hypertrophy

Frontiers in Pharmacology

Huanhuan Zhao²  Jing Yu²  Chunpeng Li²  Zihao Li²  Xiaoying Zhang²  Hao Wu³  Liping Wei³  Xin Qi³ 

[1]Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China

[2]Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China

[3]Nankai University School of Medicine, Tianjin, China

关键词: dapagliflozin;    cardiac hypertrophy;    AngII;    Plin5/PPARα signaling;    mice;   

DOI  :  10.3389/fphar.2021.730623

来源: DOAJ

【 摘 要 】

Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism.Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules.Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy.Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.

【 授权许可】

Unknown