title: The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of the miR-126/VEGFR2 pathway.
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.
authors.affiliation: Clinical Research Center and Department of Cardiology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China;
authors.forename: Keng
authors.initials: K
authors.lastname: Wu
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan, Hubei, China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; and.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Pharmacology and Toxicology and.
authors.forename: Hala Mustafa
authors.initials: HM
authors.lastname: Ammar
authors.affiliation: Clinical Research Center and Department of Cardiology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China;
authors.forename: Peihua
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Clinical Research Center and Department of Cardiology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China;
authors.forename: Runmin
authors.initials: R
authors.lastname: Guo
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan, Hubei, China;
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; and.
authors.forename: Chuanfang
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, Boonshoft School of Medicine, Wright State University, Dayton, Ohio.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Koroscil
authors.affiliation: Clinical Research Center and Department of Cardiology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China; Department of Pharmacology and Toxicology and Department of Internal Medicine, Boonshoft School of Medicine, Wright State University, Dayton, Ohio.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; and.
authors.forename: Shiming
authors.initials: S
authors.lastname: Liu
authors.affiliation: Clinical Research Center and Department of Cardiology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China; Department of Pharmacology and Toxicology and ji.bihl@wright.edu.
authors.forename: Ji C
authors.initials: JC
authors.lastname: Bihl
mesh_terms: D000328:Adult; D017209:Apoptosis; D016022:Case-Control Studies; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: endothelial progenitor cells; miR-126; microvesicles; oxidative stress; type 2 diabetes; vascular endothelial growth factor receptor 2