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| Item Type: | Preprint |
|---|---|
| Title: | Targeting Runx1 protects against heart failure with preserved ejection fraction |
| Creators Name: | Elbassioni, A.A.M., Raheem, A.A., Song, J., Johnston, A.S., Trivett, C., Lin, H., Zhang, H., Bradley, A., Higgins, E., Mooney, L., Koay, Y.C., O'Toole, D., Herzyk, P., Nixon, C., Blyth, K., O'Sullivan, J.F., Lang, N.N., Berry, C., Braun, T., Schiattarella, G.G., Giacca, M., McBride, M.W., Nicklin, S.A., Cameron, E.R., Loughrey, C.M. and MacDonald, E.A. |
| Abstract: | Heart failure with preserved ejection fraction (HFpEF) is a public health problem and an elusive illness for which there are few 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. Master-regulator transcription factor RUNX1 has recently been identified as a mediator of pathological changes in many cardiac diseases, however its role in HFpEF was unknown. 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 inhibitors improves diastolic function, both in female and male mice. Overall, our research enhances our understanding of RUNX1 in cardiac disease and demonstrates a novel translational target for the treatment of HFpEF. |
| Keywords: | Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.01.24.634831 |
| Date: | 27 January 2025 |
| Official Publication: | https://doi.org/10.1101/2025.01.24.634831 |
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