Diabetic nephropathy alters the distribution of circulating angiogenic microRNAs among extracellular vesicles, HDL, and ago-2
العنوان: | Diabetic nephropathy alters the distribution of circulating angiogenic microRNAs among extracellular vesicles, HDL, and ago-2 |
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المؤلفون: | Jacques M.G.J. Duijs, Johannes H.M. Levels, Ronald W. A. L. Limpens, Wendy Stam, Rienk Nieuwland, Yanan Wang, Marlies E.J. Reinders, Roel Bijkerk, Ton J. Rabelink, Anton Jan van Zonneveld, Barend W. Florijn, Yuana Yuana, Yu Wah Au, Geesje M. Dallinga-Thie, Anita N. Böing |
المساهمون: | Experimental Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Laboratory for Experimental Clinical Chemistry, ACS - Microcirculation |
المصدر: | Diabetes, 68(12), 2287-2300. American Diabetes Association Inc. Diabetes Diabetes, 68(12), 2287-2300. AMER DIABETES ASSOC |
بيانات النشر: | American Diabetes Association, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Renal function, 030209 endocrinology & metabolism, Inflammation, Diabetic nephropathy, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, microRNA, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Circulating MicroRNA, Renal Insufficiency, Chronic, Aged, Chemistry, Middle Aged, medicine.disease, In vitro, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Argonaute Proteins, Biomarker (medicine), Female, medicine.symptom, Lipoproteins, HDL, Biomarkers, Homeostasis, Glomerular Filtration Rate |
الوصف: | 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 m2), and patients with DN (eGFR 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). |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 0012-1797 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::387d4d366da8549361705ed0af939751Test https://hdl.handle.net/1887/3630645Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....387d4d366da8549361705ed0af939751 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 00121797 |
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