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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2018

Open Access 01-12-2018 | Original investigation

MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes

Authors: Marco Witkowski, Termeh Tabaraie, Daniel Steffens, Julian Friebel, Andrea Dörner, Carsten Skurk, Mario Witkowski, Bernd Stratmann, Diethelm Tschoepe, Ulf Landmesser, Ursula Rauch

Published in: Cardiovascular Diabetology | Issue 1/2018

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Abstract

Background

Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia and inflammatory cytokines induce vascular circulating tissue factor (TF) that promotes pro-thrombotic conditions in diabetes. It has recently become evident that alterations of the post-transcriptional regulation of TF via specific microRNA(miR)s, such as miR-126, contribute to the pathogenesis of diabetes and its complications. The endothelial miR-19a is involved in vascular homeostasis and atheroprotection. However, its role in diabetes-related thrombogenicity is unknown. Understanding miR-networks regulating procoagulability in diabetes may help to develop new treatment options preventing vascular complications.

Methods and results

Plasma of 44 patients with known diabetes was assessed for the expression of miR-19a, TF protein, TF activity, and markers for vascular inflammation. High miR-19a expression was associated with reduced TF protein, TF-mediated procoagulability, and vascular inflammation based on expression of vascular adhesion molecule-1 and leukocyte count. We found plasma expression of miR-19a to strongly correlate with miR-126. miR-19a reduced the TF expression on mRNA and protein level in human microvascular endothelial cells (HMEC) as well as TF activity in human monocytes (THP-1), while anti-miR-19a increased the TF expression. Interestingly, miR-19a induced VCAM expression in HMEC. However, miR-19a and miR-126 co-transfection reduced total endothelial VCAM expression and exhibited additive inhibition of a luciferase reporter construct containing the F3 3′UTR.

Conclusions

While both miRs have differential functions on endothelial VCAM expression, miR-19a and miR-126 cooperate to exhibit anti-thrombotic properties via regulating vascular TF expression. Modulating the post-transcriptional control of TF in diabetes may provide a future anti-thrombotic and anti-inflammatory therapy.
Appendix
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Metadata
Title
MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes
Authors
Marco Witkowski
Termeh Tabaraie
Daniel Steffens
Julian Friebel
Andrea Dörner
Carsten Skurk
Mario Witkowski
Bernd Stratmann
Diethelm Tschoepe
Ulf Landmesser
Ursula Rauch
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2018
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-018-0678-z

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