LDL extracellular vesicle coagulation protein levels change after initiation of statin therapy. Findings from the METEOR trial

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:271

Article

Verbree-Willemsen, Laura¹  Zhang, Ya-Nan^2,3  Gijsberts, Crystel M.^4,5  Schoneveld, Arjan H.⁴  Wang, Jiong-Wei^2,3  Lam, Carolyn S. P.^6,7  Vernooij, Floor^2,3  Bots, Michiel L.¹  Peelen, Linda M.^1,8  Grobbee, Diederick E.¹  Raichlen, Joel S.⁹  de Kleijn, Dominique P. V.^2,3,4,5,10 

[1] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore, Singapore

[3] Natl Univ Heart Ctr Singapore, Cardiovasc Res Inst, Singapore, Singapore

[4] Univ Utrecht, Univ Med Ctr Utrecht, Expt Cardiol Lab, Utrecht, Netherlands

[5] Univ Utrecht, Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands

[6] Natl Heart Ctr Singapore, Duke NUS Grad Med Sch, Singapore, Singapore

[7] Univ Med Ctr Groningen, Cardiol, Groningen, Netherlands

[8] Univ Utrecht, Univ Med Ctr Utrecht, Dept Anesthesiol, Utrecht, Netherlands

[9] AstraZeneca, Clin Dept, Wilmington, DE USA

[10] Univ Utrecht, Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands

关键词: Coagulation;    Statin;    Extracellular vesicles;    Low-density lipoprotein;    Plasminogen;    von Willebrand factor;   

DOI  :  10.1016/j.ijcard.2018.05.098

来源: Elsevier

【 摘 要 】

Background: Statins are thought to have pleiotropic properties, including anticoagulant effects, in addition to reducing lipoprotein (LDL) levels. Plasma extracellular vesicles (EVs) are small bilayer membrane vesicles involved in various biological processes including coagulation. Since subsets of EVs in the LDL plasma fraction (LDL-EVs) correlate with thrombin activity, we hypothesized that changes in LDL-EVs after statin therapy may differ from that of serum levels of coagulation proteins, providing insight into the effects of statins on coagulation. Methods: The study was conducted in 666 subjects with available serum from the METEOR trial, a trial of the effect of rosuvastatin versus placebo in patients with subclinical atherosclerosis. Changes in protein levels of von Willebrand Factor (VWF), SerpinC1 and plasminogen were measured in serum and in LDL-EVs, and were compared between the rosuvastatin and placebo groups. Results: LDL-EV levels of plasminogen and VWF increased with rosuvastatin treatment compared to placebo (mean change of 126 +/- 8 versus 17 +/- 12 mu g/mL for plasminogen (p < 0.001) and 310 +/- 60 versus 64 +/- 55 mu g/mL for VWF (p= 0.015)). There was no difference between groups for change in LDL-EV-SerpinC1. In contrast, serum plasminogen levels increased to a lesser extent with rosuvastatin compared to placebo (23 +/- 29 versus 67 +/- 17 mu g/mL, p= 0.024) and serum VWF levels showed no significant difference between both groups. Conclusions: Rosuvastatin increases LDL-EV coagulation proteins plasminogen and VWF in patients with subclinical atherosclerosis, an effect that is different from the effect of rosuvastatin on the same proteins in serum. This identifies LDL-EVs as a newly detected possible intermediate between statin therapy and coagulation. (c) 2018 The Authors. Published by Elsevier B.V.

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