Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo
المؤلفون: 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
المصدر: Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-19 (2019)
بيانات النشر: BMC, 2019.
سنة النشر: 2019
المجموعة: LCC:Medicine
مصطلحات موضوعية: AV shunt, Shear stress, Microarray, Chemokines, Medicine
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1479-5876
Relation: http://link.springer.com/article/10.1186/s12967-019-1767-9; https://doaj.org/toc/1479-5876
DOI: 10.1186/s12967-019-1767-9
URL الوصول: https://doaj.org/article/479c1439e1c544fc8e61cfb4826b5177
رقم الانضمام: edsdoj.479c1439e1c544fc8e61cfb4826b5177
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14795876
DOI:10.1186/s12967-019-1767-9