CC BY-NC-ND 4.0 · Thromb Haemost 2019; 119(08): 1295-1310
DOI: 10.1055/s-0039-1683409
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Lysophosphatidylcholine is a Major Component of Platelet Microvesicles Promoting Platelet Activation and Reporting Atherosclerotic Plaque Instability

Philipp Diehl
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
2  Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center – University of Freiburg, University of Freiburg, Freiburg, Germany
,
Frederik Nienaber
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Maria T. K. Zaldivia
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Johannes Stamm
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Patrick M. Siegel
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
2  Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center – University of Freiburg, University of Freiburg, Freiburg, Germany
,
Natalie A. Mellett
3  Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Marius Wessinger
2  Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center – University of Freiburg, University of Freiburg, Freiburg, Germany
,
Xiaowei Wang
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
James D. McFadyen
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Nicole Bassler
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Gerhard Puetz
4  Institute for Clinical Chemistry and Laboratory Medicine, University of Freiburg, Freiburg, Germany
,
Nay M. Htun
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
David Braig
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
5  Department of Plastic and Hand Surgery, University of Freiburg, Freiburg, Germany
,
Jonathon Habersberger
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Thomas Helbing
2  Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center – University of Freiburg, University of Freiburg, Freiburg, Germany
,
Steffen U. Eisenhardt
5  Department of Plastic and Hand Surgery, University of Freiburg, Freiburg, Germany
,
Maria Fuller
6  Centre for Molecular Pathology, University of Adelaide, Adelaide, Australia
,
Christoph Bode
2  Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center – University of Freiburg, University of Freiburg, Freiburg, Germany
,
Peter J. Meikle
3  Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Yung Chih Chen
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Karlheinz Peter
1  Department of Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
› Author Affiliations
Funding P.D. was funded by scholarships from the German Research Foundation (DFG, DI 1623/1–1) and Monash University in Melbourne (Australia), J.D.M. and N.M.H. were funded by Royal Australasian College of Physicians research establishment fellowships, S.U.E. was funded by a professorial Heisenberg Fellowship from the German Research Foundation (DFG) and X.W. and Y.C.C. were funded by a fellowship from the Heart Foundation of Australia. P.J.M. and K.P. were funded by fellowships from the National Health and Medical Research Council (NHMRC) of Australia. The project was also supported in part by the Victorian Government's OIS Program.
Further Information

Publication History

16 September 2018

25 January 2019

Publication Date:
02 August 2019 (online)

  

Abstract

Background Microvesicles (MVs) are small cell-derived vesicles, which are mainly released by activated cells. They are part of a communication network delivering biomolecules, for example, inflammatory molecules, via the blood circulation to remote cells in the body. Platelet-derived MVs are known to induce vascular inflammation. Research on the mediators and mechanisms of their inflammatory effects has attracted major interest. We hypothesize that specific lipids are the mediators of vascular inflammation caused by platelet-derived MVs.

Methods and Results Liquid chromatography electrospray ionization–tandem mass spectrometry was used for lipid profiling of platelet-derived MVs. Lysophosphatidylcholine (LPC) was found to be a major component of platelet-derived MVs. Investigating the direct effects of LPC, we found that it induces platelet activation, spreading, migration and aggregation as well as formation of inflammatory platelet–monocyte aggregates. We show for the first time that platelets express the LPC receptor G2AR, which mediates LPC-induced platelet activation. In a mouse model of atherosclerotic plaque instability/rupture, circulating LPC was detected as a surrogate marker of plaque instability. These findings were confirmed by matrix-assisted laser desorption ionization imaging, which showed that the LPC concentration of human plaques was highest in vulnerable plaque regions.

Conclusion LPC is a major component of platelet-derived MVs and via its interaction with G2AR on platelets contributes to platelet activation, spreading, migration and aggregation and ultimately to vascular inflammation. Circulating LPC reports on atherosclerotic plaque instability in mice and is significantly increased in unstable areas of atherosclerotic plaques in both mice and humans, linking LPC to plaque instability.

Note

An abstract of this paper was presented at the ISTH Congress, July 6–10, 2019 in Melbourne, Australia.


Supplementary Material