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

There are currently no pharmacological therapies for calcific aortic valve disease (CAVD). Here, we evaluated the role of protein tyrosine phosphatase 1B (PTP1B) inhibition in CAVD. Up-regulation of PTP1B was critically involved in calcified human aortic valve, and PTP1B inhibition had beneficial effects in preventing fibrocalcific response in valvular interstitial cells and LDLR-/- mice. In addition, we reported a novel function of PTP1B in regulating mitochondrial homeostasis by interacting with the OPA1 isoform transition in valvular interstitial cell osteogenesis. Thus, these findings have identified PTP1B as a potential target for preventing aortic valve calcification in patients with CAVD. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

This study evaluated the role of protein tyrosine phosphatase 1B (PTP1B) inhibition in calcific aortic valve disease (CAVD). The findings showed that up-regulation of PTP1B was involved in calcification of the aortic valve and PTP1B inhibition had beneficial effects in preventing fibrocalcific response. Additionally, PTP1B was found to regulate mitochondrial homeostasis in valvular interstitial cell osteogenesis. These findings suggest that PTP1B could be a potential target for preventing aortic valve calcification in patients with CAVD.