Format

Send to

Choose Destination
J Am Coll Cardiol. 2015 Nov 3;66(18):2005-2015. doi: 10.1016/j.jacc.2015.07.081.

Development of Long Noncoding RNA-Based Strategies to Modulate Tissue Vascularization.

Author information

1
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
2
Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg, Eppendorf, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Hamburg/Kiel/Lübeck, Germany.
3
Department of Bioinformatics, University of Würzburg, Würzburg, Germany.
4
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
5
Department of Bioinformatics, University of Würzburg, Würzburg, Germany; Institute of Human Genetics, University of Würzburg, Würzburg, Germany.
6
Helmholtz Centre for Infection Research, Braunschweig, Germany.
7
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany; National Heart and Lung Institute, Imperial College London, London, United Kingdom; REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany. Electronic address: thum.thomas@mh-hannover.de.

Abstract

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.

KEYWORDS:

angiogenesis; endothelial cell biology; hypoxia; lncRNA

Comment in

PMID:
26516004
PMCID:
PMC4631810
DOI:
10.1016/j.jacc.2015.07.081
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center