학술논문
Diabetic Nephropathy Alters the Distribution of Circulating Angiogenic MicroRNAs Among Extracellular Vesicles, HDL, and Ago-2.
Document Type
Academic Journal
Author
Florijn BW; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Duijs JMGJ; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Levels JH; Department of Vascular Biology, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Dallinga-Thie GM; Department of Vascular Biology, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Wang Y; Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, the Netherlands.; Boing AN; Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, and Vesicle Observation Center, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Yuana Y; Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, and Vesicle Observation Center, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Stam W; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Limpens RWAL; Section Electron Microscopy, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Au YW; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Nieuwland R; Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, and Vesicle Observation Center, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Rabelink TJ; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Reinders MEJ; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; van Zonneveld AJ; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Bijkerk R; Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands r.bijkerk@lumc.nl.; Einthoven Laboratory for Vascular and Regenerative Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Source
Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
Subject
Language
English
Abstract
Previously, we identified plasma microRNA (miR) profiles that associate with markers of microvascular injury in patients with diabetic nephropathy (DN). However, miRs circulate in extracellular vesicles (EVs) or in association with HDL or the RNA-binding protein argonaute-2 (Ago-2). Given that the EV- and HDL-mediated miR transfer toward endothelial cells (ECs) regulates cellular quiescence and inflammation, we hypothesized that the distribution of miRs among carriers affects microvascular homeostasis in DN. Therefore, we determined the miR expression in EV, HDL, and Ago-2 fractions isolated from EDTA plasma of healthy control subjects, patients with diabetes mellitus (DM) with or without early DN (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m 2 ), and patients with DN (eGFR <30 mL/min/1.73 m 2 ). Consistent with our hypothesis, we observed alterations in miR carrier distribution in plasma of patients with DM and DN compared with healthy control subjects. Both miR-21 and miR-126 increased in EVs of patients with DN, whereas miR-660 increased in the Ago-2 fraction and miR-132 decreased in the HDL fraction. Moreover, in vitro, differentially expressed miRs improved EC barrier formation (EV-miR-21) and rescued the angiogenic potential (HDL-miR-132) of ECs cultured in serum from patients with DM and DN. In conclusion, miR measurement in EVs, HDL, and Ago-2 may improve the biomarker sensitivity of these miRs for microvascular injury in DN, while carrier-specific miRs can improve endothelial barrier formation (EV-miR-21/126) or exert a proangiogenic response (HDL-miR-132).
(© 2019 by the American Diabetes Association.)
(© 2019 by the American Diabetes Association.)