在高脂血症、肥胖、动脉粥样硬化和糖尿病患者存在淋巴管功能损伤。淋巴管在组织液脂蛋白回流至血液循环发挥重要作用。淋巴管功能障碍可致HDL功能和RCT受损。SR-BI介导了淋巴管系统的HDL转运和RCT，但SR-BI如何影响毛细淋巴管微环境HDL代谢和胆固醇跨内皮转运还有待进一步研究阐明。结合本项目组前期的研究工作，我们提出：“ApoM-S1P调节毛细淋巴管SR-BI介导的组织间隙HDL重塑促胆固醇跨内皮转运”的科学假说。拟通过体内和体外实验，采用淋巴管功能损伤模型、荧光和/或放射性标记、HDL亚类分析、淋巴管生成以及受体功能干预等手段，分别验证假说机制（1）毛细淋巴管内皮SR-BI介导组织间隙HDL重塑；（2）ApoM促进组织液及淋巴液preβ-HDL的生成；（3）ApoM-S1P促淋巴管生成，增强SR-BI的胆固醇转运能力。本项目研究结果将对淋巴管功能在脂蛋白代谢中的作用提供新的认识。

Impairment of lymphatic vessels is associated with hyperlipidemia, obesity, atherosclerotic disease and diabetes. Lymphatic vessels play an important role in drainage of interstitial fluid and lipoproteins from interstitial space to circulation. Dysfunction of lymphatic vessel system is attributed to impaired function of high density lipoprotein and reverse cholesterol transport. Scavenger receptor class B, type I mediates the high density lipoprotein transportation and reverse cholesterol transport through lymphatic system. However, it is not clear that with which manners to affect metabolism of high density lipoprotein and trans-endothelial transport of cholesterol in microenvironment of lymphatic capillary. Based on our previous research work, we raise a scientific hypothesis that “ApoM-S1P Modulates Interstitial HDL Remodeling and Promotes Trans-endothelial Cholesterol Transport Through Capillary Lymphatic Endothelial SR-BI”. To test the hypothesis, we design to reveal the hypothetic mechanisms (1) remodeling of high density lipoprotein in interstitial space is modulated by scavenger receptor class B, type I of initial lymphatic vessel, (2) apolipoprotein M promotes the preβ-HDL formation in interstitial fluid and lymph, (3) ApoM-S1P induces lymphagiogenesis and promotes cholesterol transport by SR-BI. The research work is covered by employment of wildtype and genetic modified mice and in vitro investigation with methods including functional model of lymphatics, analysis of subpopulation of HDL, fluorescent and isotope labeling, lymphangiogenesis and intervention of lymphatic function. The results of this work may provide a new insight into relation of lymphatic system function to lipoprotein metabolism.