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CC BY 4.0 · TH Open 2021; 05(04): e533-e542
DOI: 10.1055/a-1682-3415
Original Article

Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Alexandra C.A. Heinzmann
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
,
Daniëlle M. Coenen
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
2   Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, United States
,
Tanja Vajen
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
3   Cardiovascular Research Laboratory, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
,
Judith M.E.M. Cosemans 
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
,
Rory R. Koenen 
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
› Author Affiliations Funding This work was supported by the Netherlands Foundation for Scientific Research (ZonMW VIDI 016.126.358), the Landsteiner Foundation for Blood Transfusion Research (LSBR Nr. 1638) awarded to R.R.K., and by the Netherlands Organization for Scientific Research (NWO) (Vidi 91716421) and the Dutch Heart Foundation (2015T79) to D.M.C. and J.M.E.M.C.
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Abstract

The cause of atherothrombosis is rupture or erosion of atherosclerotic lesions, leading to an increased risk of myocardial infarction or stroke. Here, platelet activation plays a major role, leading to the release of bioactive molecules, for example, chemokines and coagulation factors, and to platelet clot formation. Several antiplatelet therapies have been developed for secondary prevention of cardiovascular events, in which anticoagulant drugs are often combined. Besides playing a role in hemostasis, platelets are also involved in inflammation. However, it is unclear whether current antiplatelet therapies also affect platelet immune functions. In this study, the possible anti-inflammatory effects of antiplatelet medications on chemokine release were investigated using enzyme-linked immunosorbent assay and on the chemotaxis of THP-1 cells toward platelet releasates. We found that antiplatelet medication acetylsalicylic acid (ASA) led to reduced chemokine (CC motif) ligand 5 (CCL5) and chemokine (CXC motif) ligand 4 (CXCL4) release from platelets, while leukocyte chemotaxis was not affected. Depending on the agonist, αIIbβ3 and P2Y12 inhibitors also affected CCL5 or CXCL4 release. The combination of ASA with a P2Y12 inhibitor or a phosphodiesterase (PDE) inhibitor did not lead to an additive reduction in CCL5 or CXCL4 release. Interestingly, these combinations did reduce leukocyte chemotaxis. This study provides evidence that combined therapy of ASA and a P2Y12 or PDE3 inhibitor can decrease the inflammatory leukocyte recruiting potential of the releasate of activated platelets.

Keywords

platelets - chemokines - inflammation - monocytes - atherosclerosis - antiplatelet agents

Key Findings

1. Combined therapy of ASA and αP2Y12 or PDE3 inhibitor decreases platelets' proinflammatory potential of leukocyte recruitment, which appeared to depend on platelet-derived CCL5.


2. Secretion triggered via PAR1/PAR4 is most affected by antiplatelet medications.


3. As single therapy, cangrelor and ASA are comparable in reducing proinflammatory chemokine release by platelets.


Author Contributions

A.C.A.H performed experiments, analyzed data, and drafted the manuscript; T.V and D.M.C performed experiments; J.M.E.M.C provided critical reagents and intellectual input; and R.R.K. supervised this study, obtained funding, and finalized the manuscript.


Supplementary Material



Publication History

Received: 18 June 2021

Accepted: 22 October 2020

Accepted Manuscript online:
28 October 2021

Article published online:
07 December 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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