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Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets

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 platel...

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Autores principales: Heinzmann, Alexandra C.A., Coenen, Daniëlle M., Vajen, Tanja, Cosemans, Judith M.E.M., Koenen, Rory R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Georg Thieme Verlag KG 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651446/
https://www.ncbi.nlm.nih.gov/pubmed/34901735
http://dx.doi.org/10.1055/a-1682-3415
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author Heinzmann, Alexandra C.A.
Coenen, Daniëlle M.
Vajen, Tanja
Cosemans, Judith M.E.M.
Koenen, Rory R.
author_facet Heinzmann, Alexandra C.A.
Coenen, Daniëlle M.
Vajen, Tanja
Cosemans, Judith M.E.M.
Koenen, Rory R.
author_sort Heinzmann, Alexandra C.A.
collection PubMed
description 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.
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spelling pubmed-86514462021-12-09 Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets Heinzmann, Alexandra C.A. Coenen, Daniëlle M. Vajen, Tanja Cosemans, Judith M.E.M. Koenen, Rory R. TH Open 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. Georg Thieme Verlag KG 2021-10-28 /pmc/articles/PMC8651446/ /pubmed/34901735 http://dx.doi.org/10.1055/a-1682-3415 Text en 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/ ) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Heinzmann, Alexandra C.A.
Coenen, Daniëlle M.
Vajen, Tanja
Cosemans, Judith M.E.M.
Koenen, Rory R.
Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title_full Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title_fullStr Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title_full_unstemmed Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title_short Combined Antiplatelet Therapy Reduces the Proinflammatory Properties of Activated Platelets
title_sort combined antiplatelet therapy reduces the proinflammatory properties of activated platelets
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651446/
https://www.ncbi.nlm.nih.gov/pubmed/34901735
http://dx.doi.org/10.1055/a-1682-3415
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