Siglec-9/E is a cell surface receptor expressed on immune cells and can be activated by sialoglycan ligands to play an immunosuppressive role. Our previous study showed that increasing the expression of Siglec-9 (the human paralog of mouse Siglec-E) ligands maintains functionally quiescent immune cells in the bloodstream, but the biological effects of Siglec-9 ligand alteration on atherogenesis were not further explored. In the present study, we demonstrated that the atherosclerosis risk factor ox-LDL or a high-fat diet could decrease the expression of Siglec-9/E ligands on erythrocytes. Increased expression of Siglec-E ligands on erythrocytes caused by dietary supplementation with glucose (20% glucose) had anti-inflammatory effects, and the mechanism was associated with glucose intake. In high-fat diet-fed apoE^−/− mice, glucose supplementation decreased the area of atherosclerotic lesions and peripheral inflammation. These data suggested that increased systemic inflammation is attenuated by increasing the expression of Siglec-9/E ligands on erythrocytes. Therefore, Siglec-9/E ligands might be valuable targets for atherosclerosis therapy.

Siglec-9/E是免疫细胞上表达的细胞表面受体，可以被唾液酸聚糖配体激活而发挥免疫抑制作用。我们之前的研究表明，增加 Siglec-9（小鼠 Siglec-E 的人类旁系同源物）配体的表达可以维持血液中功能性静止的免疫细胞，但 Siglec-9 配体改变对动脉粥样硬化形成的生物学效应尚未进一步探讨。在本研究中，我们证明动脉粥样硬化危险因子 ox-LDL 或高脂肪饮食可以降低红细胞上 Siglec-9/E 配体的表达。膳食补充葡萄糖（20%葡萄糖）引起红细胞上Siglec-E配体表达增加具有抗炎作用，其机制与葡萄糖摄入有关。在高脂肪饮食喂养的 apoE ^−/−小鼠中，葡萄糖补充减少了动脉粥样硬化病变和周围炎症的面积。这些数据表明，增加红细胞上 Siglec-9/E 配体的表达可以减轻全身炎症的增加。因此，Siglec-9/E配体可能是动脉粥样硬化治疗的有价值的靶点。