Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

Abstract

Exosomes are nanosized lipid vesicles originating from the endosomal system that carry many macromolecules from their parental cells and play important roles in intercellular communication. The functions and underlying mechanisms of exosomes in atherosclerosis have recently been intensively studied. In this review, we briefly introduce exosome biology and then focus on advances in the roles of exosomes in atherosclerosis, specifically exosomal changes associated with atherosclerosis, their cellular origins and potential functional cargos, and their detailed impacts on recipient cells. We also discuss the potential of exosomes as biomarkers and drug carriers for managing atherosclerosis.

Keywords: atherosclerosis; biomarker; exosomes; intercellular communication; therapy.

Figure 1

Exosome-mediated intercellular communication in the progression of atherosclerosis. Exosomes could be secreted by all types of the cells involved in atherosclerosis, such as monocytes, macrophages, platelet, endothelial cells (ECs), vascular smooth muscle cells (VSMCs). Intercellular communication via exosomes occurs, transmitting signal from one cell type to another, contributing to the progression of atherosclerosis. Detailed roles of the exosomes from different origins should be different, and thus the exosomes act as either bystanders or performers in the process. ox-LDL, oxidized low-density lipoprotein.

Figure 2

Circulating exosomes as emerging biomarkers for atherosclerosis. Circulating exosomes (exo) from different cell types associated with atherosclerosis carry cargos with identities similar to their donor cells. Real-time quantitative polymerase chain reaction (RT-qPCR), proteomic, and transcriptomic profiling of these biomarkers could be used to diagnose atherosclerosis. EC, endothelial cell; Mo, monocyte; ox-LDL, oxidized low-density lipoprotein; Plt, platelet; VSMC, vascular smooth muscle cell.

Figure 3

Exosomes in atherosclerosis therapy. (A) Both native and bioengineered exosomes are promising strategies for atherosclerosis therapy. The native exosomes are derived from cells/tissues without additional manipulation. The bioengineered exosomes could be either from gene modified cells or further modified with chemical or physical manipulation after isolation. (B) The native or bioengineered exosomes are of typical structure of EVs. Compared with other nanoparticles, the exosomes have advantages of high biocompatibility. The surface of exosomes could be engineered to harbor targeting moieties, such as antibodies or other ligands, while the inside could be engineered to encapsulate cargos of interest. (C) The delivered exosomes target various cells (endothelial cells, macrophages, etc.) involved in atherosclerosis, alleviating the pathological process.