Canagliflozin regulates ferroptosis to ameliorate heart failure in rats with preserved ejection fraction

ABSTRACT: Chronic heart failure (CHF), with whether reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), is the end-stage of various cardiovascular diseases and severely affects the patients’ lifespan. There has been no effective drugs to improve clinical outcomes for a long time. Sine the recent years, as a hypoglycemic drug, sodium-glucose cotransporter 2 inhibitor (SGLT2i) has aroused great attention due to it’s cardiovascular benefits. However, the underlying mechanisms remain unclear, particularly regarding ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death in heart failure (HF). Here, we discovered and demonstrated that ferroptosis was a key mechanism in rat model of high-salt diet-induced HF, characterized by iron overloading and lipid peroxidation, which was blocked by canagliflozin administration. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for HF prevention and canagliflozin might display cardiovascular benefits through ferroptosis mitigation.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

SUBMITTER: Ma Sai  

LAB HEAD: Yifang Guo

PROVIDER: PXD029031 | Pride | 2022-05-20

REPOSITORIES: Pride