MBL调节血管内皮细胞经oxLDL-LOX1所介导自噬的机制

项目名称： MBL调节血管内皮细胞经oxLDL-LOX1所介导自噬的机制

项目编号： No.81471056

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴蔚

作者单位： 浙江大学

项目金额： 73万元

中文摘要： 动脉粥样硬化（AS）现更多被视为自身免疫性疾病。内皮细胞损伤是AS病变的始动因素，oxLDL是导致损伤的重要自身抗原，而凝集素样oxLDL受体1（LOX1）是oxLDL的主要配体。oxLDL可经由DC细胞递呈或直接由内皮细胞摄取，导致炎症反应并影响内皮细胞自噬。多种疾病的血管病变和甘露糖结合凝集素（MBL）水平相关，而我们发现中重度肥胖儿童颈动脉内中膜厚度增加，MBL水平降低，两者呈负相关，提示MBL对血管内膜可能具有保护作用，但其机制尚不明确。MBL和LOX1同属C型凝集素，体外能和oxLDL结合。因此，我们推测MBL可能通过阻断oxLDL-LOX1信号转导起作用。故本项目拟建立内皮细胞-DC-NK细胞共培养模型和LOX1敲除小鼠模型，通过细胞及分子生物学、病理学和组织化学等手段，研究MBL调节血管内皮细胞经oxLDL-LOX1所介导自噬的机制，有助于为AS早期干预提供新的依据。

中文关键词： 动脉粥样硬化；甘露糖结合凝集素；内皮细胞；凝集素样氧化型低密度脂蛋白受体1；氧化低密度脂蛋白

英文摘要： Atherosclerosis (AS) is currently considered to be mostly an autoimmune disease, endothelial dysfunction is the initial change of AS and oxLDL is an important autoantigen that leading to endothelial cells(ECs) dysfunction. oxLDL can bind to its receptor LOX1 and presented by dendritic cells (DCs) or uptaken directly by ECs, regulating cell autophagy, resulting in ECs dysfunction. MBL level related to artery damage in many diseases.We found that in obese children the carotid intima-media thickness (CIMT) increased and the blood MBL levels decreased and negatively related with CIMT. MBL is an C -type lectin as LOX1 and MBL can bind to oxLDL in vitro. Herein, we plan to clarify the effects and mechanism of MBL in regulating ECs autophay by investigating its role in inhibitting oxLDL-LOX1 binding via ECs-DCs-NK cells co-culturing and LOX1 knock-out mouse and exploring with methods of cell and molecular biology, pathology and in vivo immunohistochemistry. It will help us to understand the role of MBL in EC dysfunction during early AS and also provides new insights into the early intervention of AS.

英文关键词： artherosclerosis;mannose binding lectin;endothelial cell;LOX1;oxLDL