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

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Research

Background:

• Sialic acids are increasingly linked to atherosclerosis, but their precise roles and mechanisms remain unclear.
• Macrophages are critical in atherosclerotic plaque development, and their polarization state influences disease progression.

Purpose of the Study:

• To investigate the role of sialic acids in M1 macrophage polarization and their contribution to atherosclerosis pathogenesis.
• To elucidate the molecular mechanisms by which sialic acids influence macrophage phenotype and atherosclerotic lesion development.

Main Methods:

• In vitro studies using RAW264.7 cells to assess macrophage polarization and cytokine expression.
• In vivo studies using APOE-/- mice to evaluate the impact of sialic acids on atherosclerosis progression.
• Analysis of signaling pathways including LKB1-AMPK-Sirt3, reactive oxygen species (ROS) levels, and autophagy flux.

Main Results:

• Sialic acids promoted M1 macrophage polarization and increased proinflammatory cytokine expression in vitro.
• Sialic acids inhibited the LKB1-AMPK-Sirt3 pathway, leading to elevated intracellular ROS and impaired autophagy.
• Plasma sialic acid levels increased during atherosclerosis development in APOE-/- mice.
• Exogenous sialic acid supplementation exacerbated plaque progression and M1 macrophage differentiation in vivo.

Conclusions:

• Sialic acids promote M1 macrophage polarization, contributing to atherosclerosis pathogenesis.
• The pro-atherosclerotic effects of sialic acids are mediated by inducing mitochondrial ROS and blocking autophagy.
• Targeting sialic acids presents a potential novel therapeutic strategy for atherosclerosis.