Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles
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 sulp...
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doaj-629b26f8bb1346a69d8c072e49b21dc02020-11-25T00:51:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-12-011919410.3390/ijms19010094ijms19010094Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular VesiclesJiong-Wei Wang0Ya-Nan Zhang1Siu Kwan Sze2Sander M. van de Weg3Flora Vernooij4Arjan H. Schoneveld5Sock-Hwee Tan6Henri H. Versteeg7Leo Timmers8Carolyn S. P. Lam9Dominique P. V. de Kleijn10Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, SingaporeSchool of Biological Sciences, Nanyang Technological University, 637551 Singapore, SingaporeExperimental Cardiology Laboratory, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, SingaporeExperimental Cardiology Laboratory, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Medicine, National University of Singapore, 117599 Singapore, SingaporeEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, 2333 ZA Leiden, The NetherlandsDepartment of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsNational Heart Centre Singapore, Duke-NUS Graduate Medical School, 169857 Singapore, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, SingaporePlasma 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.https://www.mdpi.com/1422-0067/19/1/94extracellular vesicleslipoprotein particleslow-density lipoproteinLDLLDL apheresiscoagulationfibrinolysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiong-Wei Wang Ya-Nan Zhang Siu Kwan Sze Sander M. van de Weg Flora Vernooij Arjan H. Schoneveld Sock-Hwee Tan Henri H. Versteeg Leo Timmers Carolyn S. P. Lam Dominique P. V. de Kleijn |
spellingShingle |
Jiong-Wei Wang Ya-Nan Zhang Siu Kwan Sze Sander M. van de Weg Flora Vernooij Arjan H. Schoneveld Sock-Hwee Tan Henri H. Versteeg Leo Timmers Carolyn S. P. Lam Dominique P. V. de Kleijn Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles International Journal of Molecular Sciences extracellular vesicles lipoprotein particles low-density lipoprotein LDL LDL apheresis coagulation fibrinolysis |
author_facet |
Jiong-Wei Wang Ya-Nan Zhang Siu Kwan Sze Sander M. van de Weg Flora Vernooij Arjan H. Schoneveld Sock-Hwee Tan Henri H. Versteeg Leo Timmers Carolyn S. P. Lam Dominique P. V. de Kleijn |
author_sort |
Jiong-Wei Wang |
title |
Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles |
title_short |
Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles |
title_full |
Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles |
title_fullStr |
Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles |
title_full_unstemmed |
Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles |
title_sort |
lowering low-density lipoprotein particles in plasma using dextran sulphate co-precipitates procoagulant extracellular vesicles |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-12-01 |
description |
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. |
topic |
extracellular vesicles lipoprotein particles low-density lipoprotein LDL LDL apheresis coagulation fibrinolysis |
url |
https://www.mdpi.com/1422-0067/19/1/94 |
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