Salvianolic acid B ameliorates atherosclerosis via inhibiting YAP/TAZ/JNK signaling pathway in endothelial cells and pericytes
| Autor: | Wenqing Yang, Zichen Gao, Ke Pei, Du Ziwei, Yunlun Li, Jibiao Wu, Huichao Feng, Qian Zhang, Ying Yang, Danyang Wang, Chunxiao Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Survival MAP Kinase Kinase 4 MAP Kinase Signaling System Inflammation Oxidative phosphorylation WWTR1 030204 cardiovascular system & hematology medicine.disease_cause Dephosphorylation Serine Mice 03 medical and health sciences Apolipoproteins E 0302 clinical medicine medicine Animals Humans Molecular Biology Adaptor Proteins Signal Transducing Benzofurans Chemistry Endothelial Cells YAP-Signaling Proteins Cell Biology Atherosclerosis Cell biology 030104 developmental biology Gene Expression Regulation Apoptosis medicine.symptom Pericytes Acyltransferases Oxidative stress Transcription Factors Lipoprotein |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1865:158779 |
| ISSN: | 1388-1981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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