ArticleCardiovascular diabetology2024
Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1-STING axis.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunology of heart failure with preserved ejection fraction.Expert review of clinical immunology · 2025Pooled it
- The cardio-renal-metabolic role of the nod-like receptor protein-3 and senescence-associated secretory phenotype in early sodium/glucose cotransporter-2 inhibitor therapy in people with diabetes who have had a myocardial infarction.Diabetic medicine : a journal of the British Diabetic Association · 2025Trial
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Article
- Empagliflozin restores cardiac function in obese-diabetic HFpEF mice but further alters gene expression.Basic research in cardiology · 2026Article
- Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives.Journal of translational internal medicine · 2026Article
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Empagliflozin Alleviates Osteoarthritis Progression by Attenuating Inflammation, Restoring Impaired Autophagy, and Ameliorating Chondrocyte Senescence.Biomedicines · 2026Article
- Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Heart Failure with Preserved Ejection Fraction Through Regulating Macrophage Polarization Mediated by Alpha7nAChR.Cardiovascular drugs and therapy · 2026Article
- Identification and validation of STEAP3 as a ferroptosis-related biomarker in heart failure.Frontiers in cardiovascular medicine · 2026Article
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- Long-term SGLT2 inhibitor therapy improves myocardial strain and diastolic function in HFpEF: a retrospective study linking functional recovery to reduced myocardial fibrosis.Frontiers in cardiovascular medicine · 2026Article
- Mitochondrial-inflammatory coupling in HFpEF: an emerging mechanistic framework for understanding the cardioprotective effects of SGLT2 inhibitors.Frontiers in cardiovascular medicine · 2026Review
- Transcriptional regulation in cardiovascular aging.Frontiers in cardiovascular medicine · 2026Review
- Article
- Early pathological changes of coronary microvasculation in heart failure with preserved ejection fraction.BMC cardiovascular disorders · 2025Article
- Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025Review
- Cardiometabolic HFpEF with focus on type 2 diabetes mellitus.Cardiovascular diabetology · 2025Article
- Intersecting Pathways: The Impact of Philadelphia-Negative Chronic Myeloproliferative Neoplasms on the Pathogenesis and Progression of Heart Failure with Preserved Ejection Fraction.Diagnostics (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
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 administration. In addition, EMPA treatment suppressed the increase in the levels of aging markers (p16 and p21) in HFpEF hearts. Further bioinformatics analysis verified STAT1 as the hub transcription factor during pathological changes in HFpEF mice. We next treated H9C2 cells with IFN-γ, a primary agonist of STAT1 phosphorylation, to investigate whether EMPA plays a beneficial role by blocking STAT1 activation. Our results showed that IFN-γ treatment caused cardiomyocyte senescence and STAT1 activation, which were inhibited by EMPA administration. Notably, STAT1 inhibition significantly reduced cellular senescence possibly by regulating STING expression. Our findings revealed that EMPA mitigates cardiac inflammation and aging in HFpEF mice by inhibiting STAT1 activation. The STAT1-STING axis may act as a pivotal mechanism in the pathogenesis of HFpEF, especially under inflammatory and aging conditions.
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