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.
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.
Int Immunopharmacol. 2023 Jul;120:110410. doi: 10.1016/j.intimp.2023.110410. Epub 2023 Jun 3.
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.
越来越多的证据表明唾液酸与动脉粥样硬化密切相关。然而，唾液酸在动脉粥样硬化中的作用和潜在机制尚未确定。巨噬细胞是斑块进展过程中最重要的细胞之一。在这项研究中，我们研究了唾液酸在 M1 巨噬细胞极化和动脉粥样硬化发病机制中的作用。我们发现，唾液酸可以促进 RAW264.7 细胞向 M1 表型极化，从而促进体外促炎细胞因子的表达。唾液酸的促炎作用可能是由于抑制 LKB1-AMPK-Sirt3 信号通路，上调细胞内 ROS，并损害自噬溶酶体系统，阻断自噬流。在 APOE 小鼠中，血浆中的唾液酸在动脉粥样硬化的发展过程中增加。此外，外源性补充唾液酸可促进主动脉弓和主动脉窦斑块的进展，同时外周组织中巨噬细胞向 M1 型分化。这些研究表明，唾液酸可以通过诱导线粒体 ROS 和阻断自噬来促进巨噬细胞向 M1 表型极化，从而加重动脉粥样硬化，为动脉粥样硬化的治疗提供了新的策略。
