Endothelial progenitor cell-derived exosomes ameliorate endothelial dysfunction in a mouse model of diabetes

Atherosclerosis is a serious cardiovascular complication of diabetes characterized by inflammation and endothelial damage. Indeed, dysfunction of the endothelium is considered an early marker of atherosclerosis. Endothelial progenitor cells (EPCs) are prerequisites for blood vessels lined with endothelial cells (ECs), which produce many factors to regulate blood vessel function. Importantly, EPCs also repair some dysfunctions in ECs. Exosomes have been associated with the occurrence and development of disease. Here, we analyzed the microRNAs (miRNAs) contained in exosomes derived from EPCs by using next-generation sequencing. We found that most of the top 10 highest expressed miRNAs in these exosomes were related to atherosclerosis. In a mouse model of atherosclerotic diabetes, treatment with EPC-derived exosomes significantly reduced the production of diabetic atherosclerotic plaques and inflammatory factors. In an in vitro assay examining the contractility of the thoracic aorta from these mice, the addition of EPC-derived exosomes significantly ameliorated the observed endothelium-dependent contractile dysfunction. Taken together, these results indicated that EPC-derived exosomes ameliorated atherosclerotic endothelial dysfunction in a mouse model of atherosclerotic diabetes. Thus, the present study provides a potential therapeutic application of EPC-derived exosomes in cardiovascular disease.