Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

Alexandra C A Heinzmann, Daniëlle M Coenen, Tanja Vajen, Judith M E M Cosemans, Rory R Koenen

Research output: Contribution to journalArticleAcademicpeer-review

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, α IIb β 3 and P2Y 12 inhibitors also affected CCL5 or CXCL4 release. The combination of ASA with a P2Y 12 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 P2Y 12 or PDE3 inhibitor can decrease the inflammatory leukocyte recruiting potential of the releasate of activated platelets.

Original languageEnglish
Pages (from-to)e533-e542
JournalTH open : companion journal to thrombosis and haemostasis
Volume5
Issue number4
DOIs
Publication statusPublished - Oct 2021

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