Diabetic Nephropathy Alters the Distribution of Circulating Angiogenic MicroRNAs Among Extracellular Vesicles, HDL, and Ago-2

被引：43

作者：

Florijn, Barend W. ^{[1
,2
]}

Duijs, Jacques M. G. J. ^{[1
,2
]}

Levels, Johannes H. ^{[3
]}

Dallinga-Thie, Geesje M. ^{[3
]}

Wang, Yanan ^{[4
]}

Boing, Anita N. ^{[5
,6
]}

Yuana, Yuana ^{[5
,6
]}

Stam, Wendy ^{[1
,2
]}

Limpens, Ronald W. A. L. ^{[7
]}

Au, Yu Wah ^{[1
,2
]}

Nieuwland, Rienk ^{[5
,6
]}

Rabelink, Ton J. ^{[1
,2
]}

Reinders, Marlies E. J. ^{[1
,2
]}

Van Zonneveld, Anton Jan ^{[1
,2
]}

Bijkerk, Roel ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Med Ctr, Dept Internal Med Nephrol, Amsterdam, Netherlands

[2] Univ Amsterdam, Med Ctr, Einthoven Lab Vasc & Regenerat Med, Amsterdam, Netherlands

[3] Univ Amsterdam, Med Ctr, Dept Vasc Biol, Amsterdam, Netherlands

[4] Leiden Univ, Med Ctr, Dept Internal Med Endocrinol, Leiden, Netherlands

[5] Univ Amsterdam, Med Ctr, Dept Clin Chem, Lab Expt Clin Chem, Amsterdam, Netherlands

[6] Amsterdam Univ, Med Ctr, Vesicle Observat Ctr, Amsterdam, Turkey

[7] Leiden Univ, Med Ctr, Dept Cell & Chem Biol, Sect Electron Microscopy, Leiden, Netherlands

来源：

DIABETES | 2019年 / 68卷 / 12期

关键词：

ENDOTHELIAL DYSFUNCTION; MICROVASCULAR DAMAGE; RENAL FIBROSIS; EXOSOMES; EXPRESSION; CELLS; PROGRESSION; SECRETION; COMPLEXES; MARKERS;

D O I：

10.2337/db18-1360

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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).

引用

页码：2287 / 2300

页数：14

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