Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization
| Autor: | K. Breckwoldt, Christian W. Remmele, Annette Just, Jan Fiedler, Angelika Pfanne, Marcus Dittrich, Thomas Eschenhagen, Dorothee Hartmann, Ke Xiao, Thomas Thum, Robert Geffers, Tobias Müller, Arne Hansen, Thomas Dandekar, Meik Kunz |
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| Přispěvatelé: | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. |
| Rok vydání: | 2015 |
| Předmět: |
Angiogenesis
RNA-Seq angiogenesis lncRNA RNA interference microRNA Human Umbilical Vein Endothelial Cells Humans Medicine endothelial cell biology Cells Cultured Genetics Messenger RNA Neovascularization Pathologic Tissue Engineering hypoxia Sequence Analysis RNA business.industry RNA Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Long non-coding RNA Cell biology RNA Interference RNA Long Noncoding Signal transduction Cardiology and Cardiovascular Medicine business Signal Transduction |
| Zdroj: | Journal of the American College of Cardiology. 66:2005-2015 |
| ISSN: | 0735-1097 |
| Popis: | BackgroundLong noncoding ribonucleic acids (lncRNAs) are a subclass of regulatory noncoding ribonucleic acids for which expression and function in human endothelial cells and angiogenic processes is not well studied.ObjectivesThe authors discovered hypoxia-sensitive human lncRNAs via next-generation ribonucleic acid sequencing and microarray approaches. To address their functional importance in angiogenic processes, several endothelial lncRNAs were characterized for their angiogenic characteristics in vitro and ex vivo.MethodsRibonucleic acid sequencing and microarray-derived data showed specific endothelial lncRNA expression changes after hypoxia. Validation experiments confirmed strong hypoxia-dependent activation of 2 intergenic lncRNAs: LINC00323 and MIR503HG.ResultsSilencing of these lncRNA transcripts led to angiogenic defects, including repression of growth factor signaling and/or the key endothelial transcription factor GATA2. Endothelial loss of these hypoxia-driven lncRNAs impaired cell-cycle control and inhibited capillary formation. The potential clinical importance of these endothelial lncRNAs to vascular structural integrity was demonstrated in an ex vivo model of human induced pluripotent stem cell–based engineered heart tissue.ConclusionsThe authors report an expression atlas of human hypoxia-sensitive lncRNAs and identified 2 lncRNAs with important functions to sustain endothelial cell biology. LncRNAs hold great promise to serve as important future therapeutic targets of cardiovascular disease. |
| Databáze: | OpenAIRE |
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