OC 38.3 - Different contribution of monocyte- and platelet-derived microvesicles to endothelial behavior

Background: Circulating microvesicles (MVs) are recognized as both biomarkers and mediators of inflammation and endothelial dysfunction in many pathological conditions, including cardiovascular diseases. The two main MV-subsets mediating these effects are those derived from monocytes and platelets (PLT), although the specific contribution of each of them is not well defined.

Aims: To assess how MVs released from PLT and monocytes influence processes involved in the vessel damage -i.e. oxidative stress, inflammation, leukocyte-endothelial adhesion.

Methods: PLT and monocytes were isolated from healthy subjects (HS, n=10) and acute myocardial infarction patients (AMI; n=10). MVs, spontaneously released from AMI cells and those from stimulated HS-platelet (TRAP-6 20 µM, 30 min, 37°C) and -monocytes (LPS 10µg/ml, 16h, 37°C) were isolated, characterized by flow cytometry, and added to the culture medium of human vascular endothelial cells (hECV). Superoxide anion production, inflammatory markers (IL6, TNFalpha, NF-κB mRNA expression), and hECV adhesiveness after MVs challenge were evaluated.

Results: Incubation of hECV with MVs released by activated PLT and monocytes triggered an oxidative burst (3-fold increase) in a MV concentration-dependent manner. Monocyte-MVs doubled IL6, TNFalpha, and NF-κB mRNA expression and monocyte-endothelial adhesion which were only slightly influenced by PLT-MVs. Interestingly, only AMI PLT-MVs were able to affect both the redox state and the inflammatory phenotype (two-fold increase). Conversely, AMI-monocyte-MVs upregulated hECV ICAM gene expression and twice the number of adhering monocytes. These functional effects were paralleled by an antigenic signature which reflected the overall activation status of parental cells, which results in an increased release of procoagulant and PLT-Psel+ and monocyte-CD16+-derived MVs compared to HS spontaneously-released MVs.

Conclusion(s): These data provide evidence that MVs derived from activated PLT and monocytes differently affect endothelial behavior. These functional effects mirror those induced by microvesicles spontaneously released by platelets and monocytes from AMI patients and support the antiplatelet treatment in this clinical setting.