Exosomes are nanovesicles released from cells through exocytosis and are known to be mediators of proximal as well as distant cell-to-cell signaling. They are surrounded by a classical bilayered membrane with an exceptionally high cholesterol/phospholipid ratio. Exosomes were first described in 1977, then named prostasomes, and in 1987 the name exosome was coined. Exosomes contain surface proteins, some of which can act as labels in order to find their target cells. Exosomes also contain messages in the form of proteins and nucleic acids (RNA and DNA) that are transferable to target cells. Little is known and written about cardiac exosomes, although Gupta and Knowlton described exosomes containing HSP60 in 2007. It is now known that exosomes from cardiomyocytes can transfect other cells and that the metabolic milieu of the parental cell decides the quality of exosomes released such that they induce differential gene expression in transfected cells. Future clinical use of exosomes in diagnosis, monitoring disease progress, and treatment is promising.

The immune system represents a promising novel target for prevention of atherosclerosis. Several pilot vaccines that reduce atherosclerosis in experimental animals have been developed. The aluminum hydroxide adjuvant Alum has been shown to have antiatherogenic properties in itself, suggesting that it may be a suitable adjuvant in possible future atherosclerosis vaccines. To characterize the immune pathways mediating this protection, we treated wild-type C57BL/6 and Apoe(-)(/)(-) mice with Alum or PBS. Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4(+)CD25(+)FoxP3(+) regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in Apoe(-)(/)(-) mice but not in C57BL/6 wild-type mice. A similar immunosuppressive phenotype was found also in 25-week-old Apoe(-)(/)(-) mice and was associated with reduced atherosclerosis. Alum precipitates recovered from the injection site of Apoe(-)(/)(-) mice contained antigens derived from oxidized LDL. These findings demonstrate that treatment of Apoe(-)(/)(-) mice with Alum results in an increase of regulatory T cells and suggest that these are activated by tolerogenic antigen-presenting cells presenting oxidized LDL antigens. Our findings provide improved mechanistic understanding of the atheroprotective properties of aluminum hydroxide adjuvants but also point to the importance of determining if hypercholesterolemia may compromise the efficacy of Alum-containing vaccines used clinically today.