Neu5Ac promotes high-fat diet-induced progression of atherosclerosis in ApoE-deficient mice

Atherosclerosis (AS) is a chronic inflammatory disorder underlying most cardiovascular events sialic acid (SIA), a terminal metabolite of glycolipid catabolism, modulates vascular injury, but its role in endothelial dysfunction remains unclear. To investigate whether N-acetylneuraminic acid (Neu5Ac) accelerates AS development. ApoE^-/- mice were fed a high-fat diet to induce AS. Lesion burden was assessed by Oil Red O staining, plaque morphology by H&E staining, reactive oxygen species and macrophage polarization by flow cytometry, and signaling alterations by Western blotting. Neu5Ac markedly amplified systemic inflammation, enhanced atherosclerotic plaque formation, and disrupted lipid homeostasis. Neu5Ac exacerbates AS through pro-inflammatory, pro-lipid, and chemotactic/angiogenic mechanisms, highlighting potential therapeutic targets.