Pharmacological Inhibition of Valosin-Containing Protein (VCP) Triggers Cardiac Hypertrophy and Heart Failure in Vivo

knockout phenotypes. Early developmental inhibition (24-72 hpf) led to severe cardiac impairment and apoptosis, whereas inhibition during late development (72-120 hpf) induced ventricular hypertrophy with preserved contractile function, suggesting a developmental stage-dependent effect. Furthermore, Vcp inhibition was associated with markers of disrupted proteostasis, suggesting UPS dysfunction and ER stress activation. These findings establish a zebrafish model of VCP-related cardiomyopathy, highlight its role in cardiac proteostasis and hypertrophic remodeling, and provide novel insights into disease mechanisms and potential therapeutic targets.