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bioRxiv · 10.64898/2026.07.23.740419

Restoring Klf9 Expression with Pressure Overload Leads to Metabolic Maladaptation and Early Onset of Heart Failure

Venkatasubramanian, A.·Thakkar, C.·Yang, Z.·Ivessa, A.·Sayed, N.·Abdellatif, M.·Sayed, D.
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Abstract

Klf9 is a cardiac-enriched transcription factor of the Kruppel-like factor (Klf) family. Klf9 levels decrease during cardiac hypertrophy; however, no studies have examined its transcriptional targets or role in the progression of hypertrophy. Here, we report genome-wide differential Klf9 occupancy during cardiac hypertrophy, with a predominant enrichment at the metabolic gene promoters. Further, using conditional Klf9 knock-in mice subjected to pressure overload for 1 or 2 weeks, we show that restoring Klf9 expression initially inhibits hypertrophy but later leads to early-onset heart failure. We conclude that a decrease in Klf9 is required for metabolic adaptations that support the development of compensatory hypertrophy.

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Venkatasubramanian, A., Thakkar, C., Yang, Z., Ivessa, A., Sayed, N., Abdellatif, M., Sayed, D.. 2026-07-24. Restoring Klf9 Expression with Pressure Overload Leads to Metabolic Maladaptation and Early Onset of Heart Failure. https://doi.org/10.64898/2026.07.23.740419

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