Salvianolic acid B ameliorates atherosclerosis via inhibiting YAP/TAZ/JNK signaling pathway in endothelial cells and pericytes
Salvianolic acid B ameliorates atherosclerosis via inhibiting YAP/TAZ/JNK signaling pathway in endothelial cells and pericytes
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DOI：
10.1016/j.bbalip.2020.158779
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发表时间：
2020-10-01
影响因子：
4.8
通讯作者：
Li, Yunlun
中科院分区：
文献类型：
--
作者：
Yang, Ying;Pei, Ke;Li, Yunlun
动脉粥样硬化（AS）是一种动脉壁慢性疾病，先天性和适应性免疫炎症机制都参与其中。炎症在动脉粥样硬化各阶段的病理过程中发挥着重要作用。 Yes相关蛋白（YAP）和具有PDZ结合基序的转录共激活因子（TAZ，也称为WWTR1）是抗动脉粥样硬化的新型药物靶点。因此，本研究探讨YAP/TAZ与炎症和AS的机制关系。实验表明，氧化低密度脂蛋白（ox-LDL）诱导的EC和周细胞中丝氨酸去磷酸化和YAP核转位增加，而抑制YAP会降低下游炎症因子的表达。通过应用 Sal-B，EC 和周细胞中 YAP/TAZ 和炎症蛋白（JNK、NF-κ B 和 TNF-α）的表达受到抑制。此外，Sal-B 还可以保护 EC 和周细胞免受氧化应激和细胞凋亡的影响。在体内，Sal-B 减少了面部和主动脉根窦病变的大小，并降低了高脂饮食 ApoE(-/-) 小鼠血清样本中炎症相关因子（IL-6、IL-1β、TNF-α）和 ox-LDL 的表达。因此，我们的工作提供了利用Sal-B减轻动脉粥样硬化发展的潜在治疗策略，Sal-B的抗动脉粥样硬化作用与调节YAP/TAZ/JNK信号通路有关。
Atherosclerosis (AS) is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation plays an important role in the pathological process of atherosclerosis at various stages. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) behave as a novel drug target against atherosclerosis. Therefore, the mechanism relationship of YAP/TAZ, inflammation and AS was explored in this study. Experiments demonstrated that serine dephosphorylation and nuclear translocation of YAP was increased in ECs and pericytes induced by oxidative low-density lipoprotein (ox-LDL), while the inhibition of YAP degraded the expression of downstream inflammatory factors. The expression of YAP/TAZ and inflammation proteins (JNK, NF-kappa B and TNF-alpha) in ECs and pericytes was suppressed through the application of Sal-B. Besides, Sal-B protects ECs and pericytes from oxidative stress and apoptosis. In vivo, Sal-B reduced en face and aortic root sinus lesions size, and decreased the expression of inflammation related factors (IL-6, IL-1 beta, TNF-alpha) and ox-LDL in serum sample of ApoE(-/-) mice fed a high fat diet. Therefore, our work provides a potential therapeutic strategy of using Sal-B to attenuate the development of atherosclerosis, the anti-atherosclerosis effects of Sal-B is related to regulate YAP/TAZ/JNK signaling pathway.