Exosomes are the smallest vesicles (50-90 nm) and are released constitutively or in response to cell activation by fusion of multivesicular bodies with the plasma membrane. Thus, exosomes have an endosomal origin that is reflected in their molecular composition (Mittelbrunn and Sanchez-Madrid 2012; Thery et al. 2002). Numerous studies have confirmed the presence of an miRNA and mRNA pool in exosomes, and a novel mechanism of genetic exchange between cells was proposed (Valadi
2007). In the vasculature, endothelial-derived exosomes were shown to mediate transfer of miR-143 and miR-145 to smooth muscle cells and elicit an atheroprotec- tive response (Hergenreider et al. 2012), while an exosome-mediated cross talk between endothelial cells was recently reported to result in the delivery of miR-214 to recipient endothelial cells, an essential step to suppress senescence and stimulate migration and angiogenesis (Van Balkom et al. 2013).
In the heart, a novel paracrine mechanism of miRNA exchange between cardiac fibroblasts and cardiomyocytes was uncovered. Intriguingly, it was mediated by the star strand of the miRNA duplex. Exosome mediated transfer of miR-21-targeted sorbin and SH3 domain-containing protein 2 (SORBS2) and PDZ and LIM domain 5 (PDLIM5) expressions in the recipient cardiomyocytes and that led to cardiac hypertrophy. Remarkably, cardiomyocyte-derived exosomes can control endothelial cell proliferation, migration and angiogenic potential. MiR-320 transfer was proposed to mediate this response, with exosomes from cardiomyocytes in a rat model of type 2 diabetes eliciting an inhibitory effect on angiogenesis (Wang et al. 2014).