Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G725-G735. doi: 10.1152/ajpgi.00340.2019. Epub 2020 Feb 18.
Recently, peripheral lymphatic vessels were found to transport high-density lipoprotein (HDL) from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is thought to be critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely understood. This study aimed to ) determine the contribution of the lymphatics draining the intestine and liver (which are major sites of HDL synthesis) to total (thoracic) lymph HDL transport and ) verify whether the HDLs in lymph are derived from specific organs and are modified during trafficking in lymph. The mesenteric, hepatic, or thoracic lymph duct was cannulated in nonfasted Sprague-Dawley rats, and lymph was collected over 5 h under anesthesia. Whole lymph and specific lymph lipoproteins (isolated by ultracentrifugation) were analyzed for protein and lipid composition. The majority of thoracic lymph fluid, protein, and lipid mass was sourced from the mesenteric, and to a lesser extent, hepatic lymph. Mesenteric and thoracic lymph were both rich in chylomicrons and very low-density lipoprotein, whereas hepatic lymph and plasma were HDL-rich. The protein and lipid mass in thoracic lymph HDL was mostly sourced from mesenteric lymph, whereas the cholesterol mass was equally sourced from mesenteric and hepatic lymph. HDLs were compositionally distinct across the lymph sources and plasma. The composition of HDL also appeared to be modified during passage from the mesenteric and hepatic to the thoracic lymph duct. Overall, this study demonstrates that the lipoproteins in lymph are organ specific in composition, and the intestine and liver appear to be the main source of HDL in the lymph. High-density lipoprotein in lymph are organ-specific in composition and derive mostly from the intestine and liver. High-density lipoprotein also appears to be remodeled during transport through the lymphatics. These findings have implications to cardiometabolic diseases that involve perturbations in lipoprotein distribution and metabolism.
最近，在胆固醇逆向转运过程中发现外周淋巴管将高密度脂蛋白（HDL）从间质组织转运到血液循环中。这一功能被认为对清除动脉粥样硬化斑块中的胆固醇至关重要。然而，器官特异性淋巴管在调节 HDL 转运和组成方面的作用尚未完全了解。本研究旨在：1）确定引流肠道和肝脏（HDL 合成的主要部位）的淋巴管对总（胸）部淋巴 HDL 转运的贡献；2）验证淋巴中的 HDL 是否来源于特定器官，并在淋巴运输过程中发生修饰。在非禁食 Sprague-Dawley 大鼠中对肠系膜、肝或胸导管进行套管插管，在麻醉下收集 5 小时的淋巴。对全淋巴和特定的淋巴脂蛋白（通过超速离心分离）进行蛋白和脂质组成分析。大部分胸淋巴液、蛋白和脂质来源于肠系膜，其次是肝淋巴。肠系膜和胸淋巴均富含乳糜微粒和极低密度脂蛋白，而肝淋巴和血浆富含 HDL。胸淋巴 HDL 的蛋白和脂质主要来源于肠系膜淋巴，而胆固醇主要来源于肠系膜和肝淋巴。胸淋巴 HDL 的蛋白和脂质组成在不同来源的淋巴和血浆中均有不同。HDL 的组成在通过肠系膜和肝至胸导管的过程中似乎也发生了修饰。总体而言，本研究表明，淋巴中的脂蛋白在组成上具有器官特异性，肠道和肝脏似乎是淋巴中 HDL 的主要来源。淋巴中的 HDL 在组成上具有器官特异性，主要来源于肠道和肝脏。HDL 在通过淋巴管运输过程中似乎也发生了重塑。这些发现对涉及脂蛋白分布和代谢紊乱的心血管代谢疾病具有重要意义。
