The Modulatory Role of Circulating Microvesicles in Endothelial Progenitor Cell Function is Altered in T2DM
Ji C. Bihl (Committee Member), Yanfang Chen (Advisor), David Cool (Committee Member)
Master of Science (MS)
Circulating microvesicles (cMVs) are the extracellular MVs released from the cells in the blood and on the vascular wall. Our previous study demonstrates that cMVs of diabetic mouse are detrimental to endothelial progenitor cells (EPCs), which are known to be very important for maintaining normal endothelial function and structure. In this study, we compared the levels of circulating EPCs and EPC-derived MVs (EPC-MVs) in diabetic and healthy subjects. Also, the migration ability, apoptosis rate and reactive oxygen species (ROS) production of EPCs cultured from diabetic and healthy subjects were determined. More importantly, we evaluated whether cMVs from healthy subjects (ch-MVs) improves the function of EPCs from diabetic patients (d-EPCs), and whether cMVs from diabetic patients (cd-MVs) impairs the function of EPCs from healthy subjects (h-EPCs). The d-EPCs or h-EPCs were incubated with ch-MVs or cd-MVs for 24 hours. The migration ability of EPCs was analyzed by an assay kit. The apoptotic rate and ROS production were analyzed by labeling with propidium iodide (PI) and dihydroethidium (DHE) respectively, followed with flow cytometeric analysis. Our data showed that (1) there was a decrease in EPCs iv and an elevation in EPC-MVs in diabetic patients when compared to healthy subjects; (2) The migration ability of d-EPCs were decreased, and the apoptosis rate and ROS production were increased in d-EPCs; (3) ch-MVs improve the function of d-EPC through improving its migration ability and decreasing the apoptosis and ROS production; (4) cd-MVs increase h-EPC apoptosis, and increase ROS production. We conclude that cMVs modulate EPC function and this role of cMVs is reversed in diabetes with the mechanism linked to ROS production.
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
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