Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1-STING axis.

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed a high-fat diet (HFD) supplemented with L-NAME for 12 weeks and subsequently intraperitoneally injected with EMPA for another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes in the failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. HFpEF group) and 173 DEPs (HFpEF vs. EMPA group). The regulation of immune system processes was enriched in all groups and the interferon response genes (STAT1, Ifit1, Ifi35 and Ifi47) were upregulated in HFpEF mice but downregulated after EMPA administra

SUBMITTER: Shi Y 

PROVIDER: S-EPMC11267814 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature