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Article
The Effects of Microvesicles on Endothelial Progenitor Cells are Compromised in Type 2 Diabetic Patients via Downregulation of the miR-126/VEGFR2 Pathway
American Journal of Physiology - Endocrinology and Metabolism
  • Keng Wu
  • Yi Yang
  • Yun Zhong
  • Hala Mustafa Ammar, Wright State University - Main Campus
  • Peihua Zhang
  • Runmin Guo
  • Hua Liu
  • Chuanfang Cheng
  • Thomas M. Koroscil, Wright State University
  • Yanfang Chen, Wright State University - Main Campus
  • Shiming Liu
  • Ji C. Bihl, Wright State University - Main Campus
Document Type
Article
Publication Date
5-15-2016
Abstract

Our previous study showed that circulating microvesicles (cMVs) of diabetic mice have negative effects on the function of endothelial progenitor cells (EPCs). Whether this is true in diabetic patients deserves further study. 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.

DOI
10.1152/ajpendo.00056.2016
Citation Information
Keng Wu, Yi Yang, Yun Zhong, Hala Mustafa Ammar, et al.. "The Effects of Microvesicles on Endothelial Progenitor Cells are Compromised in Type 2 Diabetic Patients via Downregulation of the miR-126/VEGFR2 Pathway" American Journal of Physiology - Endocrinology and Metabolism Vol. 310 Iss. 10 (2016) p. E828 - E837 ISSN: 01931849
Available at: http://works.bepress.com/ji_bihl/36/