Inhibiting RhoA Activation Via GDP-State Stabilization to Relieve Heart Failure - PubMed

3 hours ago

Heart failure (HF) remains a major health concern with high morbidity and mortality, necessitating new therapeutic strategies.
RhoA, a small GTPase, plays a crucial role in myocardial remodeling but has been considered undruggable due to its high-affinity binding to GDP/GTP.
A natural product, AH001, was identified to stabilize RhoA's GDP-state by occupying a cryptic pocket, inhibiting its activation.
AH001 reduces downstream signaling, including MRTFA nuclear translocation and fibrosis/hypertrophy-related protein expression.
The compound disrupts pathological interactions between cardiomyocytes and fibroblasts, mitigating myocardial remodeling in HF models.
This study provides a framework for targeting RhoA and other small GTPases in HF therapy.

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