Exosomal microRNAs in diabetic heart disease

Figures

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  Fig. 1. Exosome biogenesis. The invagination of the cell membrane results in the formation of the early endosome (A). Various budding into the endosomal lumen, initiates the process of forming exosomes/intraluminal vesicles in the late sorting endosome (B). Cargo is shuttled between the trans-golgi network (C), endoplasmic reticulum (D)and the late sorting endosome (B). Cumulatively, this leads to the formation of a multivesicular body (E) with fully formed intraluminal vesicles/exosomes in it. The multivesicular body can be further processed within the cell by the lysosome (F) or autophagosome (G) to breakdown the components of the multivesicular body into the cell. Otherwise, the multivesicular body can be docked (H) and fused to the cell membrane to release the exosomes (I) into the extracellular space. Exosomes can be characterized using different surface markers (J) that are consistently expressed by them. Exosomal functionality (K) is based on the varying cargo within the exosomes. Image Created with Biorender.com with valid license

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  Fig. 2. Function of exosomes under DHD conditions. Studies have been conducted on exosomes isolated from DHD biological fluids as well as from culture media under DHD conditions. Exosomes released from patients with DHD has been demonstrated to increase calcification, plaque rupture, adverse remodeling and blood pressure in the vasculature. This was mimicked in the in vitro experiments where diabetic exosomes increased endothelial cell apoptosis, while decreasing proliferation, angiogenesis and migration. Similarly, DHD exosomes in vivo resulted in increased apoptosis, fibrosis and adverse remodeling of the heart as well as reduced cell survival. Just as in in vitro experiments, DHD exosomes promoted cardiomyocyte apoptosis while reducing cardiomyocyte survival