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Int. J. Mol. Sci. 2018, 19(1), 94; doi:10.3390/ijms19010094

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

1
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, Singapore
2
Cardiovascular Research Institute, National University Heart Centre Singapore, 117599 Singapore, Singapore
3
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593 Singapore, Singapore
4
School of Biological Sciences, Nanyang Technological University, 637551 Singapore, Singapore
5
Experimental Cardiology Laboratory, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
6
Department of Medicine, National University of Singapore, 117599 Singapore, Singapore
7
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands
8
Department of Cardiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
9
National Heart Centre Singapore, Duke-NUS Graduate Medical School, 169857 Singapore, Singapore
10
Department of Cardiology, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
11
Department of Vascular Surgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
12
Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands
*
Authors to whom correspondence should be addressed.
Received: 26 October 2017 / Revised: 23 December 2017 / Accepted: 27 December 2017 / Published: 29 December 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [3390 KB, uploaded 29 December 2017]   |  

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. View Full-Text
Keywords: extracellular vesicles; lipoprotein particles; low-density lipoprotein; LDL; LDL apheresis; coagulation; fibrinolysis extracellular vesicles; lipoprotein particles; low-density lipoprotein; LDL; LDL apheresis; coagulation; fibrinolysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, J.-W.; Zhang, Y.-N.; Sze, S.K.; van de Weg, S.M.; Vernooij, F.; Schoneveld, A.H.; Tan, S.-H.; Versteeg, H.H.; Timmers, L.; Lam, C.S.P.; de Kleijn, D.P.V. Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles. Int. J. Mol. Sci. 2018, 19, 94.

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