目前没有用于钙化性主动脉瓣疾病(CAVD)的药物疗法。这里,我们评估了蛋白酪氨酸磷酸酶1B(PTP1B)抑制在CAVD中的作用。PTP1B的上调与钙化的人主动脉瓣密切相关,和PTP1B抑制在阻止瓣膜间质细胞和LDLR-/-小鼠的纤维钙化反应方面具有有益作用。此外,我们报道了PTP1B在瓣膜间质细胞成骨过程中通过与OPA1同工型转变相互作用调节线粒体稳态的新功能.因此,这些发现确定PTP1B是CAVD患者预防主动脉瓣钙化的潜在靶点.
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.