4.7 Article

Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity

期刊

JOURNAL OF EXTRACELLULAR VESICLES
卷 10, 期 6, 页码 -

出版社

WILEY
DOI: 10.1002/jev2.12084

关键词

extracellular vesicles; monocyte; platelet aggregates; proteomics; vascular inflammation

资金

  1. H2020 Marie Sklodowska-Curie Actions [675111]
  2. Irish Research Council for Science, Engineering and Technology [IRCGOIPD/2017/1060]
  3. Science Foundation Ireland [15/US/B3130, 15/IA/3152]
  4. Juvenile Diabetes Research Foundation United States of America
  5. Versus Arthritis [22235]
  6. Wellcome [101604/Z/13/Z]
  7. European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [675111]
  8. Wellcome Trust [101604/Z/13/Z]
  9. IRC Government of Ireland postdoctoral fellowship [IRC GOIPD/2017/1060]
  10. JDRF NY, USA
  11. Versus Arthritis Senior Research Fellowship [22235]
  12. Wellcome Trust [101604/Z/13/Z] Funding Source: Wellcome Trust
  13. Science Foundation Ireland (SFI) [15/IA/3152, 15/US/B3130] Funding Source: Science Foundation Ireland (SFI)
  14. Marie Curie Actions (MSCA) [675111] Funding Source: Marie Curie Actions (MSCA)

向作者/读者索取更多资源

Extracellular vesicles released by mixed aggregates of monocytes and platelets have pro-inflammatory effects on endothelial cells and atherosclerotic plaques, and modulating platelet activation can alter the composition and actions of these vesicles, potentially providing therapeutic avenues for atherosclerosis treatment. Patients with coronary artery disease requiring intervention show elevated levels of specific EV subsets in plasma.
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-alpha display pro-inflammatory actions on endothelial cells and atherosclerotic plaques. Tempering platelet activation with Iloprost, Aspirin or a P2Y(12) inhibitor impacted quantity and phenotype of EV produced. Proteomics of EVs from cells activated with TNF-alpha 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-alpha stimulated monocytes augmented release of cytokines. In contrast, EVs generated by TNF-alpha 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.

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