Key result
HDAC4 inhibitor RT2 markedly improves diastolic function and exercise capacity in HFpEF mice.
Why the study?
It remained unclear which specific HDACs inhibited by pan-HDAC inhibitors drive improvements in HFpEF, prompting investigation into whether disrupting the class IIa HDAC4 corepressor complex rescues diastolic dysfunction.
Does the allosteric HDAC4 inhibitor RT2 improve diastolic dysfunction and metabolic health in a murine HFpEF model?
Population
Murine HFpEF model induced by high fat diet plus L-NAME treatment and HDAC4-cKO mice
Comparison
Allosteric HDAC4 inhibitor RT2 vs vehicle
Design
Preclinical animal study
Authors
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Offers potential HFpEF target but should not yet change practice; extends preclinical evidence for allosteric HDAC4 inhibition.
Does the allosteric HDAC4 inhibitor RT2 improve diastolic dysfunction and metabolic health in a murine HFpEF model?
Inhibition of HDAC4 with the allosteric inhibitor RT2 reverses diastolic dysfunction and improves metabolic parameters in a murine model of HFpEF, highlighting a potential therapeutic target.
Paluvai et al. (2026) studied this question. The allosteric HDAC4 inhibitor RT2 significantly improved diastolic dysfunction (E/E’: 26.32 vs 45.54), exercise capacity (327.0 vs 200), and reduced blood glucose levels in HFpEF mice.