Exosomes: Multifaceted Messengers in Atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease that contributes to the development of coronary artery disease, which has become a leading health burden worldwide. Though several strategies such as pharmacological treatment, exercise intervention, and surgery have been used in clinical practice, there is still no effective strategy to cure AS. Exosomes are extensively studied both as diagnostic markers as well as for therapeutic purposes due to their role in pathological processes related to AS. To elucidate the role of exosomes in AS and thus provide a new insight into AS therapy, we review recent advances concerning exosome targets and their function in mediating intercellular communication in AS, and expect to provide a reference for novel effective strategies to cure AS.

Exosomes exert important roles in the diagnosis, development, and potential therapy of AS. For AS development, (1) activation of CD-137 in endothelial cells represses exosomal-TET2 production, causing a phenotypic switch of vascular smooth muscle cells (VSMC) and promoting plaque formation; (2) exosomal-MALTA1 derived from endothelial cells causes neutrophil extracellular traps (NETs) and M2 macrophage polarization, which aggravates AS; and (3) exosomal-miR-21-3p derived from macrophages inhibits PTEN expression and further promotes VSMC migration/proliferation, leading to AS development. For AS diagnosis, plasma exosomal-miR30e and miR-92a are considered to be potential diagnostic markers. For AS therapy, adipose mesenchymal stem cell-derived exosomes protect endothelial cells from AS aggravation, via inhibiting miR-342-5p. Exosome-mediated cross-talk between different cells within the vasculature exerts crucial roles in regulating endothelial function, proliferation and differentiation of vascular smooth muscle cells, and platelet activation as well as macrophage activation, collectively leading to the development and progression of AS. Exosomes can potentially be used as diagnostic biomarkers and constitute as a new therapeutic strategy for AS.