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Salvianolic acid B ameliorates atherosclerosis via inhibiting YAP/TAZ/JNK signaling pathway in endothelial cells and pericytes.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 3.9 ) Pub Date : 2020-07-31 , DOI: 10.1016/j.bbalip.2020.158779
Ying Yang 1 , Ke Pei 1 , Qian Zhang 1 , Danyang Wang 1 , Huichao Feng 1 , Ziwei Du 1 , Chunxiao Zhang 1 , Zichen Gao 1 , Wenqing Yang 1 , Jibiao Wu 1 , Yunlun Li 2
Affiliation  

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-κB and TNF-α) 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-1β, TNF-α) 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.



中文翻译:

丹酚酸B通过抑制内皮细胞和周细胞中的YAP / TAZ / JNK信号传导途径改善动脉粥样硬化。

动脉粥样硬化(AS)是一种先天性和适应性免疫炎症机制都涉及的慢性动脉壁疾病。炎症在各个阶段的动脉粥样硬化的病理过程中起着重要作用。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)可以作为对抗动脉粥样硬化的新型药物靶标。因此,本研究探讨了YAP / TAZ,炎症和AS的机制关系。实验表明,氧化性低密度脂蛋白(ox-LDL)诱导的EC和周细胞中,YAP的丝氨酸去磷酸化和核易位增加,而对YAP的抑制则降低了下游炎症因子的表达。YAP / TAZ和炎症蛋白(JNK,通过使用Sal-B可抑制EC和周细胞中的NF-κB和TNF-α。此外,Sal-B保护EC和周细胞免受氧化应激和细胞凋亡。在体内,Sal-B可减少ApoE血清样品中面部和主动脉根窦病变的大小,并降低炎症相关因子(IL-6,IL-1β,TNF-α)和ox-LDL的表达-/-小鼠喂养高脂饮食。因此,我们的工作提供了使用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。

更新日期:2020-08-10
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