@article{9e0ee78357c049079ca3882bb2ff30ad,
title = "Lowering low-density lipoprotein particles in plasma using dextran sulphate co-precipitates procoagulant extracellular vesicles",
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.",
keywords = "Coagulation, Extracellular vesicles, Fibrinolysis, LDL, LDL apheresis, Lipoprotein particles, Low-density lipoprotein",
author = "Wang, \{Jiong Wei\} and Zhang, \{Ya Nan\} and Sze, \{Siu Kwan\} and \{van de Weg\}, \{Sander M.\} and Flora Vernooij and Schoneveld, \{Arjan H.\} and Tan, \{Sock Hwee\} and Versteeg, \{Henri H.\} and Leo Timmers and Lam, \{Carolyn S.P.\} and \{de Kleijn\}, \{Dominique P.V.\}",
note = "Funding Information: Acknowledgments: The authors thank Richard Dirven (Einthoven Laboratory for Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands) for expert technical assistance to develop the procoagulant assay and Jingyi Chua and Xiaoxun Yang (Department of Medicine, National University of Singapore) for collecting and processing the blood samples. This study was supported by the National University Health System Collaborative Grant (NUHS O-CRG 2016 Oct-23) to Jiong-Wei Wang; NMRC Centre Grant to Carolyn S. P. Lam and Dominique P. V. de Kleijn; Queen of Hearts program Dutch Heart Foundation (2013T084) to Dominique P. V. de Kleijn; NMRC CS-IRG (CS-IRG13nov024) to Carolyn S. P. Lam and Dominique P. V. de Kleijn; ATTRaCT SPF grant (SPF2014/003) to Carolyn S. P. Lam and Dominique P. V. de Kleijn; NUS Startup grant and KNAW strategic grant to Dominique P. V. de Kleijn. Funding Information: The authors thank Richard Dirven (Einthoven Laboratory for Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands) for expert technical assistance to develop the procoagulant assay and Jingyi Chua and Xiaoxun Yang (Department of Medicine, National University of Singapore) for collecting and processing the blood samples. This study was supported by the National University Health System Collaborative Grant (NUHS O-CRG 2016 Oct-23) to Jiong-WeiWang; NMRC Centre Grant to Carolyn S. P. Lam and Dominique P. V. de Kleijn; Queen of Hearts program Dutch Heart Foundation (2013T084) to Dominique P. V. de Kleijn; NMRC CS-IRG (CS-IRG13nov024) to Carolyn S. P. Lam and Dominique P. V. de Kleijn; ATTRaCT SPF grant (SPF2014/003) to Carolyn S. P. Lam and Dominique P. V. de Kleijn; NUS Startup grant and KNAW strategic grant to Dominique P. V. de Kleijn. Publisher Copyright: {\textcopyright} 2017 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2018",
month = jan,
day = "1",
doi = "10.3390/ijms19010094",
language = "English",
volume = "19",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",
}