Extracellular Vesicles: Investigating the Pathophysiology of Diabetes-Associated Hypertension and Diabetic Nephropathy

SIMPLE SUMMARY: Hypertension may present before or after the onset of diabetes, but in either case, it may increase the risk of developing diabetic nephropathy, the leading cause of end-stage kidney disease. Extracellular vesicles allow for communication between different cell types, the alteration of various signaling pathways, and are involved in disease mechanisms. Various omic studies have revealed that circulating extracellular vesicles and urinary extracellular vesicles are a rich source of biomarkers and markers of the prognosis of specific kidney-associated diseases including diabetes-associated hypertension and diabetic nephropathy. ABSTRACT: Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including plasma and urine. Urinary extracellular vesicles (uEVs) are a mixed population of EVs that comprise small EVs that are filtered and excreted, EVs secreted by tubular epithelial cells, and EVs released from the bladder, urethra, and prostate. The packaged cargo within uEVs includes bioactive molecules such as metabolites, lipids, proteins, mRNAs, and miRNAs. These molecules are involved in intercellular communication, elicit changes in intracellular signaling pathways, and play a role in the pathogenesis of various diseases including diabetes-associated hypertension and diabetic nephropathy. uEVs represent a rich source of biomarkers, prognosis markers, and can be loaded with small-molecule drugs as a vehicle for delivery.