高尔基体内UDP-GalNAc水平调控内皮细胞Siglec-E配体表达变化在半乳糖减缓动脉粥样硬化形成中的机制研究

动脉粥样硬化因能导致多种严重心脑血管疾病严重危害人类健康，作为一种血管慢性炎症性疾病，局部炎症反应状态在其发展和转归中有重要作用。研究证实特异性表达在巨噬细胞和中性粒细胞上的Siglec-9/E能通过抑炎作用参与维持炎症稳态，而Siglec-9/E配体的表达水平是调控该抑炎作用强度的关键。本课题组在既往证实内皮细胞表达的Siglec-9/E配体参与维持血管炎症稳态的基础上，通过预实验发现半乳糖能够减缓模型动物动脉粥样硬化斑块形成且与该配体表达增高有关，但尚需深入研究。本项目拟在明确半乳糖影响内皮细胞Siglec-E配体表达水平及其对动脉粥样硬化形成作用的基础上，进一步探索高尔基体内UDP-GalNAc水平变化对Siglec-E配体表达水平的影响及其机制。达到从糖生物学角度深入探讨血管炎症稳态的维持机制并初步阐明半乳糖干预动脉粥样硬化形成的机制，为探索防治动脉粥样硬化新策略提供新靶点和新思路

Atherosclerosis is a fundamental pathological process responded to some life-threatening coronary artery disease and accounts for one-fifth of all deaths in the world. Atherosclerosis is considered as a chronic inflammatory disease in aorta, therefore local inflammation plays an important role in the formation of atherosclerosis. Siglec-9/E, which specifically expressed on monocyte-macrophage and neutrophil, could inhibit the inflammatory reaction of the cells. The expression level of the ligands of Siglec-9/E could modulate the effects of Siglec-9/E. Our previous study has identified Siglec-9/E ligands in endothelial and explored the anti-inflammation effects of the ligands. Furthermore, we noticed that the treatment of galactose could attenuate the formation of atherosclerosis lesion in apoE-/- mice, and the mechanism might be associated with the alteration of Siglec-9/E ligands level. In this study, we try to explore the role of Siglec-E ligands level alteration in endothelial on the effects of galactose on atherosclerosis, and then investigate the role of Golgi UDP-GalNAc level on the expression level of Siglec-E ligands. Hopefully, the novel experimental and theoretical foundation could be provided to help investigating a new therapeutic target for the atherogenesis.