| 4659 wileyonlinelibrary.com/journal/jcmm 1 | INTRODUC TI ON T helpers 17 (Th17) cells have been identified as a new subset of lymphocytes which are shown to promote atherosclerosis (AS), and their associated cytokines in the pathogenesis of AS appear to be contradictory at first glance. 1-3 Recently, growing attention has been paid to the relative contribution of the local vs. peripheral inflammation to the procession of AS. Here, we focused on the communication between peripheral inflammation and vascular inflammation of Th17 cell differentiation during AS.Exosomes are a subset of extracellular vesicles (EVs) released by almost all types of cells, and they play a significant role in cellular proliferation, apoptosis, stress response and differentiation in the initial stage and development of AS. 4,5 In the present study, we investigated exosome-mediated cell-to-cell communication, which induced Th17 cell differentiation and promoted progression of the atherosclerotic plaque.
AbstractThe role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137-modified ECs (CD137-Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti-CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137-Exo efficiently induced the progression of AS in ApoE −/− mice. CD137-Exo increased the proportion of Th17 cells both in vitro and vivo. The IL-6 contained in CD137-Exo which is regulated by Akt and NF-КB pathway was verified to activate Th17 cell differentiation. IL-17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1) and E-selectin in the supernatants of ECs after IL-17 treatment was dramatically increased. CD137-Exo promoted the progression of AS and Th17 cell differentiation via NF-КB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. K E Y W O R D S atherosclerosis, endothelial cells; Th17 cells, exosomes