The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of the miR-126/VEGFR2 pathway

In this study, the effects of cMVs and EPC-derived MVs (EPC-MVs) on EPC migration, apoptosis, and reactive oxygen species (ROS) production in healthy controls, well-controlled, and uncontrolled diabetic patients were investigated. The levels of miR-126 and vascular endothelial growth factor receptor 2 (VEGFR2) in cMVs, EPC-MVs, and/or EPCs were analyzed. Moreover, miR-126 inhibitor or mimic was applied to EPCs to modulate the miR-126 level in EPC-MVs. We found the following: 1) the circulating EPC level was reduced but the circulating EPC-MV level increased in uncontrolled diabetic patients; 2) the cMVs and EPC-MVs of healthy controls had beneficial effects on EPCs (migration, apoptosis, ROS), whereas the effects were reversely changed in the cMVs and EPC-MVs of uncontrolled diabetic patients; and 3) the cMVs and EPC-MVs of uncontrolled diabetic patients carried less miR-126 and had downregulated VEGFR2 expression in EPCs. Manipulating the miR-126 level in EPC-MVs with inhibitor or mimic changed their function. The effects of cMVs and EPC-MVs are compromised in diabetes due to the reduction of their carried miR-126, which might provide a therapy target for diabetic vascular complications.

Source: AJP: Endocrinology and Metabolism - May 14, 2016 Category: Endocrinology Authors: Wu, K., Yang, Y., Zhong, Y., Ammar, H. M., Zhang, P., Guo, R., Liu, H., Cheng, C., Koroscil, T. M., Chen, Y., Liu, S., Bihl, J. C. Tags: Articles Source Type: research