The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of the miR-126/VEGFR2 pathway.
Am J Physiol Endocrinol Metab
; 310(10): E828-37, 2016 05 15.
Article
en En
| MEDLINE
| ID: mdl-26956185
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptor 2 de Factores de Crecimiento Endotelial Vascular
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MicroARNs
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Diabetes Mellitus Tipo 2
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Micropartículas Derivadas de Células
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Células Progenitoras Endoteliales
Tipo de estudio:
Observational_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2016
Tipo del documento:
Article