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Thromb Haemost 2014; 112(06): 1277-1287
DOI: 10.1160/th14-02-0139
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome

Xavier Blanchet   *
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
,
Katja Cesarek   *
2   Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
,
Johanna Brandt
3   Statistical Consulting Unit, Department of Statistics, Ludwig-Maximilians-University, Germany
,
Heiko Herwald
4   Department of Infection Medicine, Lund University, and Lund University Hospital, Lund, Sweden
,
Daniel Teupser
5   Institute of Laboratory Medicine, Ludwig-Maximilians-University Munich, Germany
,
Helmut Küchenhoff
3   Statistical Consulting Unit, Department of Statistics, Ludwig-Maximilians-University, Germany
,
Ela Karshovska
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
,
Sebastian F. Mause
2   Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
,
Wolfgang Siess
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
,
Hermann Wasmuth
6   Medizinische Klinik, Luisenhospital, Aachen, Germany
,
Oliver Soehnlein
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
9   Department of Pathology, Academic Medical Center Amsterdam, Amsterdam University, the Netherlands
,
Rory R. Koenen
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
7   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Christian Weber
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
7   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Philipp von Hundelshausen
1   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany
8   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Author Affiliations Financial support: This study was funded by Deutsche Forschungsgemeinschaft (DFG Hu1618/1–2 and FOR809 to P.v.H, R.R.K. and C.W) and the European Research Council (ERC Advanced Grant 249929 awarded to C.W).
Further Information

Publication History

Received: 14 February 2014

Accepted after major revision: 01 July 2014

Publication Date:
29 November 2017 (online)

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Summary

Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.

Note: The review process for this paper was fully handled by Gregory Y. H. Lip, Editor in Chief.

Keywords

Acute coronary syndrome - atherosclerosis - chemokines - platelets - neutrophils

* The first two authors contributed equally to this work.


 

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