Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity
Abstract Extracellular vesicles (EVs) are emerging as key players in different stages of atherosclerosis. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF‐α display pro‐inflammatory actions on endothelial cells and atherosclerotic plaques....
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12084 |
| _version_ | 1828429235507691520 |
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| author | Silvia Oggero Monica deGaetano Simone Marcone Stephen Fitzsimons Andreia L. Pinto Dinara Ikramova Mary Barry David Burke Trinidad Montero‐Melendez Dianne Cooper Thomas Burgoyne Orina Belton Lucy V. Norling Eoin P. Brennan Catherine Godson Mauro Perretti |
| author_facet | Silvia Oggero Monica deGaetano Simone Marcone Stephen Fitzsimons Andreia L. Pinto Dinara Ikramova Mary Barry David Burke Trinidad Montero‐Melendez Dianne Cooper Thomas Burgoyne Orina Belton Lucy V. Norling Eoin P. Brennan Catherine Godson Mauro Perretti |
| author_sort | Silvia Oggero |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) are emerging as key players in different stages of atherosclerosis. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF‐α display pro‐inflammatory actions on endothelial cells and atherosclerotic plaques. Tempering platelet activation with Iloprost, Aspirin or a P2Y12 inhibitor impacted quantity and phenotype of EV produced. Proteomics of EVs from cells activated with TNF‐α alone or in the presence of Iloprost revealed a distinct composition, with interesting hits like annexin‐A1 and gelsolin. When added to human atherosclerotic plaque explants, EVs from TNF‐α stimulated monocytes augmented release of cytokines. In contrast, EVs generated by TNF‐α together with Iloprost produced minimal plaque activation. Notably, patients with coronary artery disease that required percutaneous coronary intervention had elevated plasma numbers of monocyte, platelet as well as double positive EV subsets. In conclusion, EVs released following monocyte/platelet activation may play a potential role in the development and progression of atherosclerosis. Whereas attenuating platelet activation modifies EV composition released from monocyte/platelet aggregates, curbing their pro‐inflammatory actions may offer therapeutic avenues for the treatment of atherosclerosis. |
| first_indexed | 2024-12-10T17:30:10Z |
| format | Article |
| id | doaj.art-e2e22bed7e5c4e41a80f8c691c19795d |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-12-10T17:30:10Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-e2e22bed7e5c4e41a80f8c691c19795d2022-12-22T01:39:42ZengWileyJournal of Extracellular Vesicles2001-30782021-04-01106n/an/a10.1002/jev2.12084Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivitySilvia Oggero0Monica deGaetano1Simone Marcone2Stephen Fitzsimons3Andreia L. Pinto4Dinara Ikramova5Mary Barry6David Burke7Trinidad Montero‐Melendez8Dianne Cooper9Thomas Burgoyne10Orina Belton11Lucy V. Norling12Eoin P. Brennan13Catherine Godson14Mauro Perretti15William Harvey Research Institute Bart's and the London School of Medicine Queen Mary University of London London UKDiabetes Complications Research Centre Conway Institute, & School of Medicine University College Dublin Dublin IrelandTrinity Translational Medicine Institute Trinity College Dublin Dublin IrelandDiabetes Complications Research Centre Conway Institute, & School of Medicine University College Dublin Dublin IrelandRoyal Brompton & Harefield NHS Foundation Trust London UKSchool of Engineering and Materials Science Queen Mary University of London London UKDepartment of Vascular Surgery St. Vincent's University Hospital Dublin IrelandDepartment of Vascular Surgery St. Vincent's University Hospital Dublin IrelandWilliam Harvey Research Institute Bart's and the London School of Medicine Queen Mary University of London London UKWilliam Harvey Research Institute Bart's and the London School of Medicine Queen Mary University of London London UKRoyal Brompton & Harefield NHS Foundation Trust London UKDiabetes Complications Research Centre Conway Institute, & School of Medicine University College Dublin Dublin IrelandWilliam Harvey Research Institute Bart's and the London School of Medicine Queen Mary University of London London UKDiabetes Complications Research Centre Conway Institute, & School of Medicine University College Dublin Dublin IrelandDiabetes Complications Research Centre Conway Institute, & School of Medicine University College Dublin Dublin IrelandWilliam Harvey Research Institute Bart's and the London School of Medicine Queen Mary University of London London UKAbstract Extracellular vesicles (EVs) are emerging as key players in different stages of atherosclerosis. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF‐α display pro‐inflammatory actions on endothelial cells and atherosclerotic plaques. Tempering platelet activation with Iloprost, Aspirin or a P2Y12 inhibitor impacted quantity and phenotype of EV produced. Proteomics of EVs from cells activated with TNF‐α alone or in the presence of Iloprost revealed a distinct composition, with interesting hits like annexin‐A1 and gelsolin. When added to human atherosclerotic plaque explants, EVs from TNF‐α stimulated monocytes augmented release of cytokines. In contrast, EVs generated by TNF‐α together with Iloprost produced minimal plaque activation. Notably, patients with coronary artery disease that required percutaneous coronary intervention had elevated plasma numbers of monocyte, platelet as well as double positive EV subsets. In conclusion, EVs released following monocyte/platelet activation may play a potential role in the development and progression of atherosclerosis. Whereas attenuating platelet activation modifies EV composition released from monocyte/platelet aggregates, curbing their pro‐inflammatory actions may offer therapeutic avenues for the treatment of atherosclerosis.https://doi.org/10.1002/jev2.12084extracellular vesiclesmonocyte/platelet aggregatesproteomicsvascular inflammation |
| spellingShingle | Silvia Oggero Monica deGaetano Simone Marcone Stephen Fitzsimons Andreia L. Pinto Dinara Ikramova Mary Barry David Burke Trinidad Montero‐Melendez Dianne Cooper Thomas Burgoyne Orina Belton Lucy V. Norling Eoin P. Brennan Catherine Godson Mauro Perretti Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity Journal of Extracellular Vesicles extracellular vesicles monocyte/platelet aggregates proteomics vascular inflammation |
| title | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| title_full | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| title_fullStr | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| title_full_unstemmed | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| title_short | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| title_sort | extracellular vesicles from monocyte platelet aggregates modulate human atherosclerotic plaque reactivity |
| topic | extracellular vesicles monocyte/platelet aggregates proteomics vascular inflammation |
| url | https://doi.org/10.1002/jev2.12084 |
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