P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells
Abstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and ma...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95710-3 |
| _version_ | 1818425534414061568 |
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| author | Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter |
| author_facet | Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter |
| author_sort | Patrick M. Siegel |
| collection | DOAJ |
| description | Abstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages. Using flow cytometry, migration assays, flow chambers and RNA microarrays, we investigated the effects of adenosine diphosphate (ADP) and P2Y12 receptor blockers on blood monocytes, THP-1 monocytes and THP-1 monocytes after differentiation to macrophages. P2Y12 -expressing platelets can form aggregates with monocytes in circulating blood. Mediated by platelets, ADP results in activation of the integrin receptor Mac-1 on blood monocytes, as detected by the conformation-specific single-chain antibody MAN-1. Via the same association with platelets, THP-1 monocyte adhesion to the endothelial intercellular adhesion molecule 1 (ICAM-1) is induced by ADP. P2Y12 receptor blockers prevent these ADP effects on monocytes. Interestingly, in contrast to THP-1 monocytes, THP-1 monocytes, after differentiation to macrophages, directly expressed the P2Y12 receptor and consequently ADP was found to be a potent chemoattractant. Again, P2Y12 receptor blockers antagonised this effect. Accordingly, stimulation of THP-1 macrophages with ADP caused a substantial change in gene expression pattern and upregulation of several genes associated with inflammation and atherogenesis. These data establish novel anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages, which are expected to contribute to cardiovascular risk reduction. |
| first_indexed | 2024-12-14T14:15:28Z |
| format | Article |
| id | doaj.art-02fdc9b5ec5545029a39ac063008c7a8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:15:28Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-02fdc9b5ec5545029a39ac063008c7a82022-12-21T22:58:12ZengNature PortfolioScientific Reports2045-23222021-08-0111111610.1038/s41598-021-95710-3P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cellsPatrick M. Siegel0Laura Sander1Alba Fricke2Johannes Stamm3Xiaowei Wang4Prerna Sharma5Nicole Bassler6Ya-Lan Ying7Christoph B. Olivier8Steffen U. Eisenhardt9Christoph Bode10Ingo Ahrens11Philipp Diehl12Karlheinz Peter13Department of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteDepartment of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes InstituteDepartment of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgDepartment of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgDepartment of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgDepartment of Cardiology and Angiology I, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, University of FreiburgAbstract P2Y12 blockade improves patient outcomes after myocardial infarction. As well as antithrombotic effects, anti-inflammatory effects may contribute to this beneficial clinical outcome. Here we aimed to identify potential anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages. Using flow cytometry, migration assays, flow chambers and RNA microarrays, we investigated the effects of adenosine diphosphate (ADP) and P2Y12 receptor blockers on blood monocytes, THP-1 monocytes and THP-1 monocytes after differentiation to macrophages. P2Y12 -expressing platelets can form aggregates with monocytes in circulating blood. Mediated by platelets, ADP results in activation of the integrin receptor Mac-1 on blood monocytes, as detected by the conformation-specific single-chain antibody MAN-1. Via the same association with platelets, THP-1 monocyte adhesion to the endothelial intercellular adhesion molecule 1 (ICAM-1) is induced by ADP. P2Y12 receptor blockers prevent these ADP effects on monocytes. Interestingly, in contrast to THP-1 monocytes, THP-1 monocytes, after differentiation to macrophages, directly expressed the P2Y12 receptor and consequently ADP was found to be a potent chemoattractant. Again, P2Y12 receptor blockers antagonised this effect. Accordingly, stimulation of THP-1 macrophages with ADP caused a substantial change in gene expression pattern and upregulation of several genes associated with inflammation and atherogenesis. These data establish novel anti-inflammatory effects of P2Y12 receptor blockers on monocytes and macrophages, which are expected to contribute to cardiovascular risk reduction.https://doi.org/10.1038/s41598-021-95710-3 |
| spellingShingle | Patrick M. Siegel Laura Sander Alba Fricke Johannes Stamm Xiaowei Wang Prerna Sharma Nicole Bassler Ya-Lan Ying Christoph B. Olivier Steffen U. Eisenhardt Christoph Bode Ingo Ahrens Philipp Diehl Karlheinz Peter P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells Scientific Reports |
| title | P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells |
| title_full | P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells |
| title_fullStr | P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells |
| title_full_unstemmed | P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells |
| title_short | P2Y12 receptor blockers are anti-inflammatory drugs inhibiting both circulating monocytes and macrophages including THP-1 cells |
| title_sort | p2y12 receptor blockers are anti inflammatory drugs inhibiting both circulating monocytes and macrophages including thp 1 cells |
| url | https://doi.org/10.1038/s41598-021-95710-3 |
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