Liu Feng, Chen Jinyong, Hu Wangxing, Gao Chenyang, Zeng Zhiru, Cheng Si, Yu Kaixiang, Qian Yi, Xu Dilin, Zhu Gangjie, Zhao Jing, Liu Xianbao, Wang Jian'an
Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Cardiovascular Disease of Zhejiang Province, Hangzhou, China.
JACC Basic Transl Sci. 2022 Jul 25;7(7):697-712. doi: 10.1016/j.jacbts.2022.03.002. eCollection 2022 Jul.
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.
目前尚无针对钙化性主动脉瓣疾病（CAVD）的药物治疗方法。在此，我们评估了蛋白酪氨酸磷酸酶1B（PTP1B）抑制在CAVD中的作用。PTP1B的上调在人类钙化主动脉瓣中起关键作用，并且PTP1B抑制在预防瓣膜间质细胞和低密度脂蛋白受体（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异构体转变相互作用来调节线粒体稳态的新功能。因此，这些发现已将PTP1B确定为预防CAVD患者主动脉瓣钙化的潜在靶点。
