Silvia Oggero, Ph.D.
Queen Mary University of London
Ph.D. in Biochemical Pharmacology
Summary: Released by virtually every cell, extracellular vesicles (EVs) can contribute to development and progression of cardiovascular diseases by promoting vascular inflammation processes like endothelial dysfunction or unstable plaque progression. Here we focus on the role EVs released from monocyte-platelet aggregates, predicting they may elicit pathogenic actions. Heterogeneous subsets of EVs, studied by imaging-flow cytometry, nanoparticle tracking analysis and proteomics, can be released by monocytes-platelets aggregates in response to TNF-α. Moreover, inhibition of platelet activation upon addition of a prostacyclin analogue can influence the type of EVs released. Human Umbilical Vein Endothelial Cells treated with EVs showed increased expression of ICAM-1 and VCAM-1 and this led to a higher PMN recruitment in an in-vitro flow-chamber assay. In an ex-vivo model of atherosclerosis, fragments of human atherosclerotic plaques incubated with EVs increased levels of secreted pro-inflammatory cytokines as part of an overall distinct proteome released in response to application of EVs. Finally, EV levels were checked in plasma samples of patients with essential hypertension and higher levels of EV subsets identified with this work was predictive of cardiovascular events or death. Altogether, these results suggest that EV heterogeneity reflects the mode of activation of cells of origin and may differently contribute to development and progression of cardiovascular diseases.