Diabetic Nephropathy Alters the Distribution of Circulating Angiogenic MicroRNAs Among Extracellular Vesicles, HDL,

Barend W Florijn1,2, Jacques M G J Duijs1,2, Johannes H Levels3

  • 1Department of Internal Medicine (Nephrology), Amsterdam University Medical Center, Amsterdam, the Netherlands.

Diabetes
|September 12, 2019
PubMed

Insights

Plasma microRNA (miR) distribution in extracellular vesicles (EVs), HDL, and Ago-2 is altered in diabetic nephropathy (DN). Specific miRs in these carriers impact endothelial cell function, offering potential biomarkers for microvascular injury.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nephrology

Background:

  • Plasma microRNA (miR) profiles are linked to microvascular injury in diabetic nephropathy (DN).
  • MicroRNAs (miRs) are transported via extracellular vesicles (EVs), HDL, and argonaute-2 (Ago-2).
  • EV- and HDL-mediated miR transfer influences endothelial cell (EC) quiescence and inflammation.

Purpose of the Study:

  • To investigate how miR distribution among carriers (EVs, HDL, Ago-2) affects microvascular homeostasis in diabetic nephropathy (DN).
  • To identify specific miRs and their carriers associated with DN and their functional impact on endothelial cells.

Main Methods:

  • Isolation of EV, HDL, and Ago-2 fractions from EDTA plasma of healthy controls, diabetes mellitus (DM) patients with/without early DN, and DN patients.
  • Quantification of miR expression within these isolated fractions.
  • In vitro assessment of differentially expressed miRs on endothelial cell barrier formation and angiogenic potential.

Main Results:

  • Significant alterations in miR carrier distribution were observed in patients with DM and DN compared to controls.
  • miR-21 and miR-126 increased in EVs of DN patients.
  • miR-660 increased in the Ago-2 fraction, and miR-132 decreased in the HDL fraction in DN patients.
  • In vitro studies showed EV-miR-21 improved EC barrier function and HDL-miR-132 rescued EC angiogenic potential.

Conclusions:

  • Plasma miR measurement in EVs, HDL, and Ago-2 fractions may enhance biomarker sensitivity for microvascular injury in DN.
  • Carrier-specific miRs demonstrate functional roles, with EV-miRs (miR-21/126) improving endothelial barrier formation and HDL-miR-132 promoting angiogenesis.

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