Oggero, S;
Gaetano, M;
Marcone, S;
Fitzsimons, S;
Pinto, AL;
Ikramova, D;
Barry, M;
... Perretti, M; + view all
(2021)
Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity.
Journal of Extracellular Vesicles
, 10
(6)
, Article 12084. 10.1002/jev2.12084.
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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.
| Type: | Article |
|---|---|
| Title: | Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jev2.12084 |
| Publisher version: | http://dx.doi.org/10.1002/jev2.12084 |
| Language: | English |
| Additional information: | © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | extracellular vesicles, monocyte/platelet aggregates, proteomics, vascular inflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10127110 |
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