Extracellular vesicles are a heterogeneous family of vesicles, generated from different subcellular compartments and released into the extracellular space. Composed of a lipid bilayer encompassing both soluble cytosolic material and nuclear components, these organelles have been recently described as novel regulators of intercellular communication between adjacent and remote cells. Due to their diversified composition and biological content, they portray specific signatures of cellular activation and pathological processes, their potential as diagnostic and prognostic biomarkers has raised significant interest in cardiovascular diseases. Circulating vesicles, especially those released from platelets, leukocytes, and endothelial cells are found to play a critical role in activating several fundamental cells within the vasculature, including endothelial cells and vascular smooth muscle cells. Their intrinsic activity and immunomodulatory properties lends them to not only promote vascular inflammation, but also enhance tissue regeneration, vascular repair, and indeed resolution. In this review we aim to recapitulate the recent findings concerning the roles played by EVs that originate from different circulating cells, with particular reference to their action on the endothelium. We focus herein, on the interaction of platelet and leukocyte EVs with the endothelium. In addition, their potential biological function in promoting tissue resolution and vascular repair will also be discussed.

Plasma MV profiles vary according to the source of infection. A2MG MV are associated with survival in CAP but not FP. We propose specific MV subsets as novel biomarkers in sepsis and potential effector for some of the actions of experimental therapeutic interventions.

Rheumatoid arthritis-associated pain is poorly managed, often persisting when joint inflammation is pharmacologically controlled. Comparably, in the mouse K/BxN serum-transfer model of inflammatory arthritis, hind paw nociceptive hypersensitivity occurs with ankle joint swelling (5 days after immunisation) persisting after swelling has resolved (25 days after immunisation). In this study, lipid mediator (LM) profiling of lumbar dorsal root ganglia (DRG), the site of sensory neuron cell bodies innervating the ankle joints, 5 days and 25 days after serum transfer demonstrated a shift in specialised proresolving LM profiles. Persistent nociception without joint swelling was associated with low concentrations of the specialised proresolving LM Maresin 1 (MaR1) and high macrophage numbers in DRG. MaR1 application to cultured DRG neurons inhibited both capsaicin-induced increase of intracellular calcium ions and release of calcitonin gene-related peptide in a dose-dependent manner. Furthermore, in peritoneal macrophages challenged with lipopolysaccharide, MaR1 reduced proinflammatory cytokine expression. Systemic MaR1 administration caused sustained reversal of nociceptive hypersensitivity and reduced inflammatory macrophage numbers in DRG. Unlike gabapentin, which was used as positive control, systemic MaR1 did not display acute antihyperalgesic action. Therefore, these data suggest that MaR1 effects observed after K/BxN serum transfer relate to modulation of macrophage recruitment, more likely than to direct actions on sensory neurons. Our study highlights that, in DRG, aberrant proresolution mechanisms play a key role in arthritis joint pain dissociated from joint swelling, opening novel approaches for rheumatoid arthritis pain treatment.