Dataset Information

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

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.

SUBMITTER: Henn D

PROVIDER: S-EPMC6330440 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Henn Dominic D Abu-Halima Masood M Wermke Dominik D Falkner Florian F Thomas Benjamin B Köpple Christoph C Ludwig Nicole N Schulte Matthias M Brockmann Marc A MA Kim Yoo-Jin YJ Sacks Justin M JM Kneser Ulrich U Keller Andreas A Meese Eckart E Schmidt Volker J VJ

Journal of translational medicine 20190111 1

<h4>Background</h4>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.<h4>Methods</h4>AV shunts were microsurgically created in rat ...[more]

PMID: 30635008

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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