PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis

•Increased PTP1B was observed in the human calcified aortic valve leaflets and VIC osteogenesis, which indicated a novel association of PTP1B with aortic valve calcification.•MSI-1436, a specific pharmacological PTP1B inhibitor, attenuated osteogenic and myofibrogenic differentiation of VICs, which coincided with preventing aortic valve fibrocalcific disease in a diet-induced mouse model of CAVD.•Treatment of CAVD with PTP1B inhibitor mitigated the disorder of aortic jet velocity and mean gradient in vivo.•PTP1B inhibition preserved the mitochondrial biogenesis and function in VIC osteogenesis via regulating OPA1 homeostasis.