MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo. / Henn, Dominic; Abu-Halima, Masood; Wermke, Dominik; Falkner, Florian; Thomas, Benjamin; Köpple, Christoph; Ludwig, Nicole; Schulte, Matthias; Brockmann, Marc A; Kim, Yoo-Jin; Sacks, Justin M; Kneser, Ulrich; Keller, Andreas; Meese, Eckart; Schmidt, Volker J.
I: Journal of Translational Medicine, Bind 17, Nr. 22, 11.01.2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo
AU - Henn, Dominic
AU - Abu-Halima, Masood
AU - Wermke, Dominik
AU - Falkner, Florian
AU - Thomas, Benjamin
AU - Köpple, Christoph
AU - Ludwig, Nicole
AU - Schulte, Matthias
AU - Brockmann, Marc A
AU - Kim, Yoo-Jin
AU - Sacks, Justin M
AU - Kneser, Ulrich
AU - Keller, Andreas
AU - Meese, Eckart
AU - Schmidt, Volker J
PY - 2019/1/11
Y1 - 2019/1/11
N2 - 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.
AB - 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.
KW - Animals
KW - Arteriovenous Shunt, Surgical
KW - Chemokine CXCL2/metabolism
KW - Female
KW - Gene Expression Regulation
KW - Hemorheology/genetics
KW - Interleukin-1/metabolism
KW - MicroRNAs/genetics
KW - Neovascularization, Physiologic/genetics
KW - RNA, Messenger/genetics
KW - Rats, Sprague-Dawley
KW - Reproducibility of Results
KW - Signal Transduction/genetics
KW - Vascular Remodeling/genetics
KW - X-Ray Microtomography
U2 - 10.1186/s12967-019-1767-9
DO - 10.1186/s12967-019-1767-9
M3 - Journal article
C2 - 30635008
VL - 17
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 22
ER -
ID: 329565186