Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization
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Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization. / Fiedler, Jan; Breckwoldt, Kaja; Remmele, Christian W; Hartmann, Dorothee; Dittrich, Marcus; Pfanne, Angelika; Just, Annette; Xiao, Ke; Kunz, Meik; Müller, Tobias; Hansen, Arne; Geffers, Robert; Dandekar, Thomas; Eschenhagen, Thomas; Thum, Thomas.
in: J AM COLL CARDIOL, Jahrgang 66, Nr. 18, 03.11.2015, S. 2005-15.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization
AU - Fiedler, Jan
AU - Breckwoldt, Kaja
AU - Remmele, Christian W
AU - Hartmann, Dorothee
AU - Dittrich, Marcus
AU - Pfanne, Angelika
AU - Just, Annette
AU - Xiao, Ke
AU - Kunz, Meik
AU - Müller, Tobias
AU - Hansen, Arne
AU - Geffers, Robert
AU - Dandekar, Thomas
AU - Eschenhagen, Thomas
AU - Thum, Thomas
N1 - Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PY - 2015/11/3
Y1 - 2015/11/3
N2 - BACKGROUND: Long 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.OBJECTIVES: The 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.METHODS: Ribonucleic 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.RESULTS: Silencing 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.CONCLUSIONS: The 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.
AB - BACKGROUND: Long 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.OBJECTIVES: The 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.METHODS: Ribonucleic 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.RESULTS: Silencing 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.CONCLUSIONS: The 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.
KW - Cell Hypoxia
KW - Cells, Cultured
KW - Human Umbilical Vein Endothelial Cells
KW - Humans
KW - Hypoxia-Inducible Factor 1, alpha Subunit
KW - Neovascularization, Pathologic
KW - RNA Interference
KW - RNA, Long Noncoding
KW - Sequence Analysis, RNA
KW - Signal Transduction
KW - Tissue Engineering
U2 - 10.1016/j.jacc.2015.07.081
DO - 10.1016/j.jacc.2015.07.081
M3 - SCORING: Journal article
C2 - 26516004
VL - 66
SP - 2005
EP - 2015
JO - J AM COLL CARDIOL
JF - J AM COLL CARDIOL
SN - 0735-1097
IS - 18
ER -