Key result
Global Wwp1 gene deletion significantly attenuated diastolic dysfunction in mice subjected to left ventricular pressure overload, reducing the E/A ratio to 1.73 compared to 3.97 in wild-type mice.
Why the study?
HFpEF often arises from prolonged LVPO with abnormal ECM accumulation, and ECM is regulated post-transcriptionally by E 3 ubiquitin ligases such as WWP1.
Does WWP1 gene deletion reduce functional indices of HFpEF progression and ECM remodeling in a model of left ventricular pressure overload?
Does WWP1 gene deletion reduce functional indices of HFpEF progression and ECM remodeling in a model of left ventricular pressure overload?
WWP1 gene deletion attenuates diastolic dysfunction and ECM remodeling in pressure-overload hypertrophy, suggesting ubiquitin ligases as a potential therapeutic target for HFpEF.
Wwp1 deletion attenuates diastolic dysfunction in pressure-overload mice; leaves open whether WWP1 inhibition merits testing in human HFpEF.
Heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF) often arises from a prolonged LV pressure overload (LVPO) and is accompanied by abnormal extracellular matrix (ECM) accumulation. It is now recognized that the ECM is a dynamic entity that is regulated at multiple post-transcriptional levels, including the E 3 ubiquitin ligases, such as WWP1. In the present study, WWP1 deletion in the context of an LVPO stimulus reduced functional indices of HFpEF progression and determinants of ECM remodeling. Understanding and targeting the ubiquitin ligases in the context of HFpEF forms an important research direction.
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Snyder et al. (2021) studied Heart failure with preserved ejection fraction (HFpEF) / Left ventricular pressure overload (n=46). Global Wwp1 gene deletion vs. Wild-type (Wwp1+/+) was evaluated on E/A ratio at 4 weeks post-LVPO (p=<0.05). Global Wwp1 gene deletion significantly attenuated diastolic dysfunction in mice subjected to left ventricular pressure overload, reducing the E/A ratio to 1.73 compared to 3.97 in wild-type mice.
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