Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction

Author:

Ma SaiORCID,He Li-Li,Zhang Guo-Rui,Zuo Qing-Juan,Wang Zhong-Li,Zhai Jian-Long,Zhang Ting-Ting,Wang Yan,Ma Hui-Juan,Guo Yi-FangORCID

Abstract

Abstract Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due to their clear cardiovascular benefits for heart failure with preserved ejection fraction (HFpEF) since there are no effective drugs that may improve clinical outcomes for these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin. Data are available via ProteomeXchange with identifier PXD029031. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, ferritin heavy chain 1, transferrin receptor, Ferroportin 1, iron, glutathione, malondialdehyde, and 4-hydroxy-trans-2-nonenal. These findings highlight the fact that targeting ferroptosis may serve as a cardioprotective strategy for HFpEF prevention and suggest that canagliflozin may exert its cardiovascular benefits partly via its mitigation of ferroptosis.

Funder

Bureau of Science and Technology of Hebei Province

2019 Hebei Innovation Capability Promotion Project

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology,General Medicine

Reference54 articles.

1. Anker SD, Butler J, Filippatos GS, Jamal W, Salsali A, Schnee J, Kimura K, Zeller C, George J, Brueckmann M, Zannad F, Packer M (2019) EMPEROR-Preserved Trial Committees and Investigators. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail 21(10):1279–1287. https://doi.org/10.1002/ejhf.1596.

2. Baba Y, Higa JK, Shimada BK, Horiuchi KM, Suhara T, Kobayashi M, Woo JD, Aoyagi H, Marh KS, Kitaoka H, Matsui T (2018) Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol 314(3):H659–H668. https://doi.org/10.1152/ajpheart.00452.2017

3. Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB (2014) Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens 8(4):262-275.e9. https://doi.org/10.1016/j.jash.2014.01.007

4. Bayeva M, Khechaduri A, Puig S, Chang HC, Patial S, Blackshear PJ, Ardehali H (2012) mTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab 16(5):645–657. https://doi.org/10.1016/j.cmet.2012.10.001

5. Borlaug BA (2020) Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol 17:559–573. https://doi.org/10.1038/s41569-020-0363-2

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