PAR4 and extracellular vesicles

Platelets are know to release extracellular vesicles (EV). In the past, EVs were thought to contribute to cardiovascular diseases. However, newer studies found that EVs can carry anti-inflammatory microRNAs (miRNAs). Interestingly, some miRNA were shown to reduced the inflammatory state of macrophages. In our new project, we found that after short term PAR4 stimulation platelet release anti-inflammatory factors into the platelet releasate (Plt-R). This Plt-R was able to reduce NFκB activation and cytokine expression in toll-like receptor (TLR) stimulated macrophages. Interestingly, the anti-inflammatory effect of the Plt-R was mediated, in part, by the platelet EV component. We think EVs protect the anti-inflammatory mediators against destruction. Moreover, we found that different miRNAs could be responsible for the anti-inflammatory response of Plt-R. Now, we investigate the role of platelet PAR4 in anti-inflammatory responses. We propose that during normal life processes, platelet EVs limit the inflammatory reaction but under severe inflammatory conditions platelet EVs contribute to inflammatory pathologies.