Program

PO1-2-71

Microvesicles in cardiovascular inflammation: markers or mediators of cardiovascular diseases?

[Speaker] Silvia Oggero:1
[Co-author] Lucy Norling:1, Mauro Perretti:1
1:William Harvey Research Institute, Queen Mary University of London, UK

Introduction: Microvesicles (MV) are membrane bound vesicles with a diameter range from 100 to 1000 nm, shed from the surface of all cell types. They are present in all body fluids and are known to bear markers that identify their cell of origin(2). Furthermore, cells can release several subsets of vesicles with distinct components, in relation to their mode of activation. This new concept termed "microvesicle heterogeneity", raises the question as to whether these small entities might represent a new strategy for diagnosing different inflammatory diseases(3). Althoug,, in the past two decades of this century, several MV (e.g. platelets and endothelial MV) have been deeply studied, monocyte-derived MV have been poorly investigated. The objective of this project was to study human monocyte-derived MV in vitro, mimicking events that occur in inflamed vasculature.

Methods: Monocytes from blood or isolated using negative selection were stimulated with TNFalfa (50ng/ml) and PAF (1uM) and the MV profile was characterized with ImagestreamX technology and nanoparticle tracking analysis.

Results: Platelet-monocyte aggregation in blood affected the number of monocyte MV released, and in the presence of PGI2 (used to inhibit platelet activation) the levels of both monocyte and platelet MV were decreased. Similar findings were observed using isolated monocytes, where platelet and monocytes aggregated together during the isolation and the presence of MV from platelets and monocytes (double positive for CD41 and CD14) was detected. In the presence of PAF, PGI2 reduced the levels of double positive MV as well as both platelet and monocyte MV.

Conclusions: The presence of double positive MV suggests the occurrence of heterogeneity within the vesicle population formed in response to different stimuli. Unexpectedly, monocyte-derived MV levels were decreased in blood with the use of PGI2 and when purified monocytes where stimulated with PAF, suggesting their possible correlation with platelet MV and platelet activation. In line with these findings, further investigation of this heterogeneity in response to stimuli will be performed with proteomic and lipidomic analyses.

References:
(1) Hargett L and Bauer NN (2013). Pulm. Circ 3: 329-340.
(2) Giebel B (2017). Ann. Transl. Med. 5: 150

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