- 作者：Jan Fiedler ; PhD&lowast ; ; &dagger ; ; Kaja Breckwoldt ; MSc&Dagger ; ; § ; ; Christian W. Remmele ; MSc鈥?/sup> ; Dorothee Hartmann ; PhD&lowast ; ; Marcus Dittrich ; MD ; PhD鈥?/sup> ; ¶ ; ; Angelika Pfanne ; MTA&lowast ; ; Annette Just ; MTA&lowast ; ; &dagger ; ; Ke Xiao ; PhD&lowast ; ; Meik Kunz ; MSc鈥?/sup> ; Tobias Mü ; ller ; PhD鈥?/sup> ; Arne Hansen ; MD&Dagger ; ; § ; ; Robert Geffers ; PhD# ; Thomas Dandekar ; MD ; PhD鈥?/sup> ; Thomas Eschenhagen ; MD ; PhD&Dagger ; ; § ; ; Thomas Thum ; MD ; PhD&lowast ; ; &dagger ; ; &lowast ; &lowast ; ; &dagger ; &dagger ; ; thum.thomas@mh-hannover.de" class="auth_mail" title="E-mail the corresponding author
- 关键词：angiogenesis ; endothelial cell biology ; hypoxia ; lncRNA
- 刊名：Journal of the American College of Cardiology
- 出版年：2015
- 出版时间：3 November 2015
- 年：2015
- 卷：66
- 期：18
- 页码：2005-2015
- 全文大小：2164 K
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.