Dapagliflozin attenuates myocardial hypertrophy via activating the SIRT1/ HIF-1 & alpha; signaling pathway

As a sodium-glucose transporter 2 inhibitor (SGLT2i), the cardioprotective benefits of Dapagliflozin (DAPA) are now widely appreciated. However, the underlying mechanism of DAPA on angiotensin II (Ang II)-induced myocardial hypertrophy has never been evaluated. In this study, we not only investigated the effects of DAPA on Ang II-induced myocardial hypertrophy, but explored its underlying mechanisms. Mice were injected with Ang II (500 ng /kg/min) or saline solution as control, followed by intragastric administration DAPA (1.5 mg/kg/ day) or saline for four weeks. DAPA treatment alleviated the condition of decrease in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) caused by Ang II. In addition, DAPA treatment significantly alleviated Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury and hypertrophy. In mice stimulated with Ang II, the degree of myocardial fibrosis and upregulation of the markers of cardiac hypertrophy (atrial natriuretic peptide, ANP and B-type natriuretic peptide, BNP) were attenuated by DAPA. What's more, DAPA partially reversed the Ang II-induced upregulation of HIF-1a and the decrease in levels of SIRT1. Taken together, activating the SIRT1/HIF-1a signaling pathway was found to confer a protective effect against experimental myocardial hypertrophy in mice induced by Ang II, demonstrating its potential as an effective therapeutic target for pathological cardiac hypertrophy.

Automated summary

As a sodium-glucose transporter 2 inhibitor (SGLT2i), Dapagliflozin (DAPA) has been widely recognized for its cardioprotective benefits. This study explored the underlying mechanisms of DAPA on angiotensin II (Ang II)-induced myocardial hypertrophy and found that DAPA treatment can alleviate Ang II-induced cardiac injury, hypertrophy, and fibrosis. It also reversed the changes in HIF-1a and SIRT1 levels induced by Ang II. Overall, activating the SIRT1/HIF-1a signaling pathway may be an effective therapeutic target for pathological cardiac hypertrophy.