Does dapagliflozin improve mitochondrial homeostasis in HFpEF models?
Dapagliflozin provides cardioprotective effects in HFpEF by restoring mitochondrial homeostasis via the SIRT1/PGC-1α/Mfn-2 signaling axis, offering mechanistic insight into SGLT2 inhibitor benefits.
HFpE model, dapagliflozin enhances mitochondrial respiratory capacity in cardiomyocytes, indicating a direct mitochondrial regulatory effect. Mechanistically, integrative transcriptomic and experimental analyses identify the SIRT1/PGC-1α/Mitofusin-2 (Mfn-2) signaling axis as a critical pathway suppressed in HFpEF but reactivated following dapagliflozin treatment. Activation of this pathway promotes mitochondrial biogenesis and improves mitochondrial dynamics, thereby preserving cardiomyocyte homeostasis. Collectively, our findings reveal that dapagliflozin exerts cardioprotective effects in HFpEF by restoring mitochondrial homeostasis through the SIRT1/PGC-1α/Mfn-2 axis, providing mechanistic insight into SGLT2i-mediated benefits and highlighting mitochondrial regulation as a potential therapeutic strategy for HFpEF.
Zhang et al. (Thu,) studied this question.