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High concentrations of circulating extracellular vesicles (EVs) are present in the blood, and their levels and contents are altered in several disease states, including cardiovascular disease. However, the function of circulating EVs − especially the microRNAs that they contain − are poorly understood. We sought to determine the effect of secreted vesicles produced by quiescent endothelial cells (ECs) on monocyte inflammatory responses, and to assess whether transfer of microRNAs occurs between these cells.
Methods and Results
We observed that monocytes co-cultured (but not in contact) with ECs were refractory to inflammatory activation. Further characterization revealed that endothelium-derived extracellular vesicles (EC-EVs) could suppress monocyte activation, suggesting that ECs secrete anti-inflammatory vesicles that affect monocyte phenotype. Monocytes treated with EC-EVs displayed enhanced immunomodulatory responses and diminished pro-inflammatory responses. EVs isolated from mouse circulation also suppressed monocyte activation. Importantly, injection of EC-EVs in vivo repressed monocyte/macrophage activation in response to lipopolysaccharide treatment, confirming our in vitro findings. We found that several microRNAs were elevated in EC-EV-treated monocytes. In particular, miR-10a was transferred to monocytes from EC-EVs and could repress inflammatory signaling through the targeting of several components of the NF-κB pathway, including IRAK4.
Conclusion
ECs secrete anti-inflammatory microRNA-containing vesicles that can modulate monocyte activation. Our findings suggest that altered EV secretion and/or microRNA content may affect vascular inflammation in the setting of cardiovascular disease.
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