Heart failure & cardiomyopathies
Direct Actions of Dapagliflozin and Interactions with LCZ696 and Spironolactone on Cardiac Fibroblasts of Patients with Heart Failure and Reduced Ejection Fraction
Authors' conclusion
SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.
Study context
- Population
- Isolated myocardial fibroblasts from patients with heart failure and reduced ejection fraction (HFrEF)
- Participants
- 5 vs 4
- Comparison
- Dapagliflozin alone or combined with LCZ696 or spironolactone on cardiac fibroblasts
- HFrEFn = 5
- Controln = 4reference
- Outcome
- Effects of dapagliflozin alone and combined with LCZ696 or spironolactone on HFrEF myocardial fibroblast migration, heart failure (HF) marker expression and signalling pathways
Main finding
As reported in the abstract
- Dapagliflozin slowed HFrEF fibroblast migration dose-dependently and markedly decreased IL-1β, IL-6, MMP3, MMP9, GAL3 and FN1 expression
- Dapagliflozin had no effect on control fibroblasts
- Dapagliflozin effects associated with decreased phosphorylation of AKT/GSK3, PYK2 and signal transducer and activator of transcription (STAT)
- Dapagliflozin + LCZ696 further decreased migration; no significant effect on signalling pathways or biomarkers vs dapagliflozin alone
- Dapagliflozin + spironolactone did not change migration but significantly altered dapagliflozin responses on MMP9, GAL3 and IL-1b, with increased AKT/GSK3 and ERK1/2 phosphorylation
Original publication
Direct Actions of Dapagliflozin and Interactions with LCZ696 and Spironolactone on Cardiac Fibroblasts of Patients with Heart Failure and Reduced Ejection Fraction. ESC Heart Fail. Published 27 October 2022. doi:10.
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