PT  - JOURNAL ARTICLE
AU  - S Oggero
AU  - M de Gaetano
AU  - S Marcone
AU  - M Barry
AU  - T Montero-Melendez
AU  - D. Cooper
AU  - L V Norling
AU  - E P Brennan
AU  - G Godson
AU  - M Perretti
TI  - Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque responses
AID  - 10.1101/841361
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 841361
4099  - http://biorxiv.org/content/early/2019/11/13/841361.short
4100  - http://biorxiv.org/content/early/2019/11/13/841361.full
AB  - In atherosclerosis, a chronic disease characterized by lipid accumulation, fibrosis and vascular inflammation, extracellular vesicles (EVs) are emerging as key players in different stages of disease development. Here we provide evidence that EVs released by mixed aggregates of monocytes and platelets in response to TNF-α are both CD14+ and CD41+. Tempering platelet activation with Iloprost™ impacted the quality and quantity of EV produced. Proteomics of EVs from cells activated with TNF-α alone or in presence Iloprost™ revealed distinct proteome, with selective hits like gelsolin. EVs from TNF-α stimulated monocytes augmented release of cytokines, and modulated more than 500 proteins by proteomics, when added to human atherosclerotic plaques. In contrast, EVs generated by TNF-α and Iloprost™ produced minimal plaque activation. In conclusion, attenuating platelet activation has an effect on EV composition released from monocyte/platelet aggregates with downstream modulation of their pro-inflammatory actions and contribution to the development and progression of atherosclerosis.