Sialic acids promote macrophage M1 polarization and atherosclerosis by upregulating ROS and autophagy blockage

作者全名："Hu, Xuemei; Li, Yueyue; Chen, Qingyang; Wang, Tingting; Ma, Limei; Zhang, Wanping; Yu, Ruihong; Zhang, Jun; Wan, Jingyuan; Yu, Chao; Yuan, Zhiyi"

作者地址："[Hu, Xuemei; Li, Yueyue; Chen, Qingyang; Wang, Tingting; Ma, Limei; Zhang, Wanping; Yu, Ruihong; Wan, Jingyuan; Yu, Chao; Yuan, Zhiyi] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Hu, Xuemei; Li, Yueyue; Chen, Qingyang; Wang, Tingting; Ma, Limei; Zhang, Wanping; Yu, Ruihong; Zhang, Jun; Yu, Chao; Yuan, Zhiyi] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China"

通信作者："Yu, C; Yuan, ZY (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001014694900001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：120

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Sialic acids; Atherosclerosis; ROS; Macrophage polarization; Autophagy

摘要："Accumulating evidence suggests that sialic acids is closely related to atherosclerosis. However, the effects and underlying mechanisms of sialic acids in atherosclerosis have been not defined. Macrophages are one of the most important cells during plaque progression. In this study, we investigated the role of sialic acids in the M1 macrophage polarization and pathogenesis of atherosclerosis. Here we found that sialic acids can promote the polarization of RAW264.7 cells to the M1 phenotype, thereby promoting the expression of proinflammatory cytokines in vitro. The proinflammatory effect of sialic acids may result from the inhibition of LKB1-AMPK-Sirt3 signaling pathway to upregulate intracellular ROS and impairing autophagy-lysosome system to block auto-phagic flux. In the APOE-/-mice, sialic acids in plasma increased during the development of atherosclerosis. Moreover, exogenous supplement of sialic acids can promote plaque progression in aortic arch and aortic sinus being accompanied by the differentiation of macrophages into M1 type in peripheral tissues. These studies demonstrated that sialic acids can promote macrophage polarization toward the M1 phenotype to accentuate atherosclerosis via inducing mitochondrial ROS and blocking autophagy, thus providing clue to a novel thera-peutic strategy for atherosclerosis."

基金机构："Youth Fund of National Natural Science Foundation,China [81800389]; Chongqing Basic and Frontier Research Project, China [cstc2017jcyjAX0283]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0069]"

基金资助正文："Acknowledgements This work was supported by Youth Fund of National Natural Science Foundation,China (No.81800389) , Chongqing Basic and Frontier Research Project, China (No. cstc2017jcyjAX0283) , Program for Youth Innovation in Future Medicine, Chongqing Medical University (No. W0069) ."