Key result
Runx1 inhibition improves diastolic function and reduces pulmonary edema in HFpEF mice.
Why the study?
Heart failure with preserved ejection fraction has limited treatment options, and although the transcription factor RUNX1 mediates pathological changes in multiple cardiac diseases, its role in HFpEF remained unknown.
Does inhibition of Runx1 improve diastolic function and reduce adverse remodeling in a mouse model of HFpEF?
Does inhibition of Runx1 improve diastolic function and reduce adverse remodeling in a mouse model of HFpEF?
Targeting the transcription factor RUNX1 protects against diastolic dysfunction and adverse remodeling in a preclinical mouse model of HFpEF, presenting a novel translational target.
RUNX1 inhibition may merit exploration in HFpEF; hypothesis-generating in mice and should not yet change practice.
Aims Heart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence and has limited treatment options. HFpEF is a systemic condition with a broad phenotype including diastolic dysfunction, pulmonary oedema, exercise intolerance, and left ventricular (LV) hypertrophy, collectively resulting in enhanced morbidity and mortality. The transcription factor RUNX1 has recently been identified as a mediator of pathological changes in multiple cardiac diseases, however its role in HFpEF remained unknown. Methods and Results Here we show that inhibition of Runx1 limits adverse cardiac remodelling in a clinically relevant mouse model of HFpEF. Cardiomyocyte-specific tamoxifen-inducible Runx1-deficient mice with HFpEF are protected, with preservation of diastolic function, and attenuation of pulmonary oedema, exercise intolerance, and hypertrophy. Furthermore, targeting Runx1 in HFpEF by using gene transfer or small molecule inhibitor Ro5-3335 improves diastolic function and reduces pulmonary oedema, both in female and male mice. Conclusion Overall, our research enhances our understanding of RUNX1 in cardiac disease and presents a novel translational target for the treatment of HFpEF.
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Elbassioni et al. (2026) studied Heart failure with preserved ejection fraction (HFpEF). Runx1 inhibition (gene transfer or Ro5-3335) was evaluated on Diastolic function, pulmonary oedema, exercise intolerance, and hypertrophy. Inhibition of Runx1 using gene transfer or the small molecule inhibitor Ro5-3335 improved diastolic function and reduced pulmonary oedema in a mouse model of HFpEF.
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