Abstract
The prevalence of diabetes mellitus (DM) is increasing at a staggering rate around the world. In the United States, more than 30.3 million Americans have DM. Type 2 diabetes mellitus (T2DM) accounts for 91.2% of diabetic cases and disproportionately affects African Americans and Hispanics. T2DM is a major risk factor for cardiovascular disease (CVD) and is the leading cause of morbidity and mortality among diabetic patients. While significant advances in T2DM treatment have been made, intensive glucose control has failed to reduce the development of macro and microvascular related deaths in this group. This highlights the need to further elucidate the underlying molecular mechanisms contributing to CVD in the setting of T2DM. Endothelial dysfunction (ED) plays an important role in the development of diabetes-induced vascular complications, including CVD and diabetic nephropathy (DN). Thus, the endothelium provides a lucrative means to investigate the molecular events involved in the development of vascular complications associated with T2DM. microRNAs (miRNA) participate in numerous cellular responses, including mediating messages in vascular homeostasis. Exosomes are small extracellular vesicles (40-160 nanometers) that are abundant in circulation and can deliver various molecules, including miRNAs, from donor to recipient cells to facilitate cell-to-cell communication. Endothelial cells are in constant contact with exosomes (and exosomal content) that can induce a functional response. This review discusses the modulatory role of exosomal miRNAs and proteins in diabetes-induced endothelial dysfunction, highlighting the significance of miRNAs as markers, mediators, and potential therapeutic interventions to ameliorate ED in this patient group.
Highlights
Diabetes mellitus is a growing epidemic that poses a major global health threat [1]
The investigators of this study report that both endothelial cell and exosomes derived from mouse brain endothelial cells contain high levels of miR-126, in comparison to exosomes derived from smooth muscle cells, marrow stromal cells, and astrocytes [53]
They go on to show that exosomes enriched with miR-20b-5p from Type 2 Diabetes Mellitus (T2DM) can transfer this miRNA into human umbilical vascular endothelial cells (HUVECs) to suppress the angiogenic effects by inhibiting Wnt9b/ß-catenin signaling pathway [51]
Summary
Diabetes mellitus is a growing epidemic that poses a major global health threat [1]. The 10th edition of the International Diabetes Federation (IDF) Diabetes Atlas estimates that 527 million people have diabetes [1]. In endothelial colony-forming cells isolated from peripheral blood of diabetic patients, Luo et al found an increased expression of miR-139-5p [35] The findings of these studies support the use of circulating miRNAs as markers of disease and suggest that circulating miRs may be useful prognostic tools in diabetes mellitus and its complications (Table 1). Since these early reports on circulating miRNAs as noninvasive markers of disease, researchers have made meaningful strides in understanding how and why extracellular miRNAs are exported from cells in physiological and pathophysiological states, especially during the diabetic milieu. One sophisticated way miRNAs are transported out of the cell involves trafficking of membrane vesicles, which was initially described by Valadi et al in 2007 [40]
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