Canagliflozin ameliorates ferritinophagy in HFpEF rats
Sai MA1
Qing-Juan ZUO2
Li-Li HE2
Guo-Rui ZHANG3
Ting-Ting ZHANG2
Zhong-Li WANG4
Jian-Long ZHAI5
Yi-Fang GUO2
1.Department of Internal Medicine,Hebei General Hospital,Shijiazhuang,Hebei,China2.Department of Geriatric Cardiology,Hebei General Hospital,Shijiazhuang,Hebei,China3.Department of Cardiology,the Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University,Shijiazhuang,Hebei,China4.Department of Physical Exam-ination Center,Hebei General Hospital,Shijiazhuang,Hebei,China5.Department of Cardiology,Hebei General Hos-pital,Shijiazhuang,Hebei,China
摘要：Background Recent studies have shown that sodium-glucose cotransporters-2(SGLT2)inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction(HFpEF)patients,but the exact mechanism is un-known.Ferritinophagy is a special form of selective autophagy that participates in ferroptosis.In this study,we aimed to invest-igate whether ferritinophagy was activated during the occurrence of HFpEF,and whether canagliflozin(CANA)could inhibite ferritinophagy.
Methods We reared Dahl salt-sensitive(DSS)rats on a high-salt diet to construct a hypertensive HFpEF model,and simultan-eously administered CANA intervention.Then we detected indicators related to ferritinophagy.
Results The expression of nuclear receptor coactivator 4(NCOA4),as well as microtubule-associated proteins light chain 3(LC3),Bcl-2 interacting protein 1(Beclin-1)and p62,were upregulated in HFpEF rats,accompanied by the downregulation of fer-ritin heavy chain 1(FTH1),upregulation of mitochondrial iron transporter sideroflexin1(SFXN1)and increased reactive oxygen species(ROS)production.Above changes were diminished by CANA.
CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA,leading to HFpEF benefits.The inhibi-tion of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF,and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.
机标关键词：canagliflozinratsamelioratesferritinophagyhfpef
论文发表日期：2025-01-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 178-189 )