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利用硫酸葡聚糖共沉淀促凝细胞外囊泡降低血浆中低密度脂蛋白颗粒。

Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles.

机构信息

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, Singapore.

Cardiovascular Research Institute, National University Heart Centre Singapore, 117599 Singapore, Singapore.

出版信息

Int J Mol Sci. 2017 Dec 29;19(1):94. doi: 10.3390/ijms19010094.

DOI:10.3390/ijms19010094
PMID:29286309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5796044/
Abstract

Plasma extracellular vesicles (EVs) are lipid membrane vesicles involved in several biological processes including coagulation. Both coagulation and lipid metabolism are strongly associated with cardiovascular events. Lowering very-low- and low-density lipoprotein ((V)LDL) particles via dextran sulphate LDL apheresis also removes coagulation proteins. It remains unknown, however, how coagulation proteins are removed in apheresis. We hypothesize that plasma EVs that contain high levels of coagulation proteins are concomitantly removed with (V)LDL particles by dextran sulphate apheresis. For this, we precipitated (V)LDL particles from human plasma with dextran sulphate and analyzed the abundance of coagulation proteins and EVs in the precipitate. Coagulation pathway proteins, as demonstrated by proteomics and a bead-based immunoassay, were over-represented in the (V)LDL precipitate. In this precipitate, both bilayer EVs and monolayer (V)LDL particles were observed by electron microscopy. Separation of EVs from (V)LDL particles using density gradient centrifugation revealed that almost all coagulation proteins were present in the EVs and not in the (V)LDL particles. These EVs also showed a strong procoagulant activity. Our study suggests that dextran sulphate used in LDL apheresis may remove procoagulant EVs concomitantly with (V)LDL particles, leading to a loss of coagulation proteins from the blood.

摘要

血浆细胞外囊泡 (EVs) 是参与包括凝血在内的多种生物学过程的脂质膜囊泡。凝血和脂质代谢都与心血管事件密切相关。通过葡聚糖硫酸盐 LDL 吸附去除极低密度脂蛋白 ((V)LDL) 颗粒也会去除凝血蛋白。然而，尚不清楚在吸附过程中如何去除凝血蛋白。我们假设，含有高水平凝血蛋白的血浆 EVs 与 (V)LDL 颗粒一起通过葡聚糖硫酸盐吸附被去除。为此，我们用葡聚糖硫酸盐从人血浆中沉淀 (V)LDL 颗粒，并分析沉淀中凝血蛋白和 EVs 的丰度。通过蛋白质组学和基于珠子的免疫测定法证明，凝血途径蛋白在 (V)LDL 沉淀中过度表达。在该沉淀中，通过电子显微镜观察到双层 EVs 和单层 (V)LDL 颗粒。使用密度梯度离心将 EVs 与 (V)LDL 颗粒分离，结果表明几乎所有的凝血蛋白都存在于 EVs 中，而不存在于 (V)LDL 颗粒中。这些 EVs 还表现出强烈的促凝活性。我们的研究表明，LDL 吸附中使用的葡聚糖硫酸盐可能会与 (V)LDL 颗粒一起去除促凝 EVs，导致血液中凝血蛋白的丢失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/397bea97fa34/ijms-19-00094-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/a988fac77eb1/ijms-19-00094-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/397bea97fa34/ijms-19-00094-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/a988fac77eb1/ijms-19-00094-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/5e2d1998be42/ijms-19-00094-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b06/5796044/7efe2da046c4/ijms-19-00094-g003.jpg
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