2. Academic Validation
  3. Sialic acids promote macrophage M1 polarization and atherosclerosis by upregulating ROS and autophagy blockage

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

  • Int Immunopharmacol. 2023 Jun 2;120:110410. doi: 10.1016/j.intimp.2023.110410.
Xuemei Hu 1,  Yueyue Li 1,  Qingyang Chen 1,  Tingting Wang 1,  Limei Ma 1,  Wanping Zhang 1,  Ruihong Yu 1,  Jun Zhang 2,  Jingyuan Wan 3,  Chao Yu 4,  Zhiyi Yuan 5
Affiliations

Affiliations

  • 1 College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
  • 2 Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
  • 3 College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
  • 4 College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China. Electronic address: yuchao@cqmu.edu.cn.
  • 5 College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China. Electronic address: yuanzhiyi-06@cqmu.edu.cn.
PMID: 37270929 DOI: 10.1016/j.intimp.2023.110410
Abstract

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 autophagic 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 therapeutic strategy for atherosclerosis.

Keywords

Atherosclerosis; Autophagy; Macrophage polarization; ROS; Sialic acids.

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