The experimental aim of this study was to determine the effects of high glucose-induced endothelial microparticles (EMPs) on endothelial cell susceptibility to apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultured (3rd passage) and plated in 6-well plates at a density of 5.0 x 10(5) cells/condition. Cells were incubated with media containing 25 mM D-glucose (concentration representing a diabetic glycemic state) or 5 mM D-glucose (normoglycemic condition) for 48 h to generate EMPs. EMP identification (CD144(+) expression) and concentration was determined by flow cytometry. HUVECs (3 x 10(6) cells/condition) were treated with EMPs generated from either the normal or high glucose conditions for 24 h. Intracellular concentration of active caspase-3 was determined by enzyme immunoassay. Cellular expression of miR-Let7a, an anti-apoptotic microRNA, was determined by RT-PCR using the Delta Delta CT normalized to RNU6. High glucose-derived EMPs significantly increased both basal (1.5 +/- 0.1 vs 1.0 +/- 0.1 ng/mL) and staurosporine-stimulated (2.2 +/- 0.2 vs 1.4 +/- 0.1 ng/mL) active caspase-3 compared with normal glucose EMPs. Additionally, the expression of miR-Let-7a was markedly reduced (similar to 140%) by high glucose EMPs (0.43 +/- 0.17 fold vs control). These results demonstrate that hyperglycemic-induced EMPs increase endothelial cell active caspase-3. This apoptotic effect may be mediated, at least in part, by a reduction in miR-Let-7a expression. (C) 2017 Elsevier Inc. All rights reserved.