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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Arteriovenous Fistula | Research

MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo

Authors: Dominic Henn, Masood Abu-Halima, Dominik Wermke, Florian Falkner, Benjamin Thomas, Christoph Köpple, Nicole Ludwig, Matthias Schulte, Marc A. Brockmann, Yoo-Jin Kim, Justin M. Sacks, Ulrich Kneser, Andreas Keller, Eckart Meese, Volker J. Schmidt

Published in: Journal of Translational Medicine | Issue 1/2019

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Abstract

Background

Vascular shear stress promotes endothelial cell sprouting in vitro. The impact of hemodynamic forces on microRNA (miRNA) and gene expression within growing vascular networks in vivo, however, remain poorly investigated. Arteriovenous (AV) shunts are an established model for induction of neoangiogenesis in vivo and can serve as a tool for analysis of hemodynamic effects on miRNA and gene expression profiles over time.

Methods

AV shunts were microsurgically created in rats and explanted on postoperative days 5, 10 and 15. Neoangiogenesis was confirmed by histologic analysis and micro-computed tomography. MiRNA and gene expression profiles were determined in tissue specimens from AV shunts by microarray analysis and quantitative real-time polymerase chain reaction and compared with sham-operated veins by bioinformatics analysis. Changes in protein expression within AV shunt endothelial cells were determined by immunohistochemistry.

Results

Samples from AV shunts exhibited a strong overexpression of proangiogenic cytokines, oxygenation-associated genes (HIF1A, HMOX1), and angiopoetic growth factors. Significant inverse correlations of the expressions of miR-223-3p, miR-130b-3p, miR-19b-3p, miR-449a-5p, and miR-511-3p which were up-regulated in AV shunts, and miR-27b-3p, miR-10b-5p, let-7b-5p, and let-7c-5p, which were down-regulated in AV shunts, with their predicted interacting targets C–X–C chemokine receptor 2 (CXCR2), interleukin-1 alpha (IL1A), ephrin receptor kinase 2 (EPHA2), synaptojanin-2 binding protein (SYNJ2BP), forkhead box C1 (FOXC1) were present. CXCL2 and IL1A overexpression in AV shunt endothelium was confirmed at the protein level by immunohistochemistry.

Conclusions

Our data indicate that flow-stimulated angiogenesis is determined by an upregulation of cytokines, oxygenation associated genes and miRNA-dependent regulation of FOXC1, EPHA2 and SYNJ2BP.
Appendix
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Metadata
Title
MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo
Authors
Dominic Henn
Masood Abu-Halima
Dominik Wermke
Florian Falkner
Benjamin Thomas
Christoph Köpple
Nicole Ludwig
Matthias Schulte
Marc A. Brockmann
Yoo-Jin Kim
Justin M. Sacks
Ulrich Kneser
Andreas Keller
Eckart Meese
Volker J. Schmidt
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-1767-9

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