Imperial College London
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Professor Costanza Emanueli

Faculty of Medicine, National Heart & Lung Institute

Chair in Cardiovascular Science
 
 
 
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Contact

 

c.emanueli Website

 
 
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Location

 

434ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Besnier:2019:10.1016/j.omtn.2019.05.002,
author = {Besnier, M and Shantikumar, S and Anwar, M and Dixit, P and Chamorro-Jorganes, A and Sweaad, W and Sala-Newby, G and Madeddu, P and Thomas, AC and Howard, L and Mushtaq, S and Petretto, E and Caporali, A and Emanueli, C},
doi = {10.1016/j.omtn.2019.05.002},
journal = {Molecular Therapy : Nucleic Acids},
pages = {49--62},
title = {miR-15a/-16 inhibit angiogenesis by targeting the Tie2 coding sequence: Therapeutic potential of a miR-15a/16 decoy system in limb ischemia.},
url = {http://dx.doi.org/10.1016/j.omtn.2019.05.002},
volume = {17},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - MicroRNA-15a (miR-15a) and miR-16, which are transcribed from the miR-15a/miR-16-1 cluster, inhibit post-ischemic angiogenesis. MicroRNA (miRNA) binding to mRNA coding sequences (CDSs) is a newly emerging mechanism of gene expression regulation. We aimed to (1) identify new mediators of the anti-angiogenic action of miR-15a and -16, (2) develop an adenovirus (Ad)-based miR-15a/16 decoy system carrying a luciferase reporter (Luc) to both sense and inhibit miR-15a/16 activity, and (3) investigate Ad.Luc-Decoy-15a/16 therapeutic potential in a mouse limb ischemia (LI) model. LI increased miR-15a and -16 expression in mouse muscular endothelial cells (ECs). The miRNAs also increased in cultured human umbilical vein ECs (HUVECs) exposed to serum starvation, but not hypoxia. Using bioinformatic tools and luciferase activity assays, we characterized miR-15a and -16 binding to Tie2 CDS. In HUVECs, miR-15a or -16 overexpression reduced Tie2 at the protein, but not the mRNA, level. Conversely, miR-15a or -16 inhibition improved angiogenesis in a Tie2-dependent manner. Local Ad.Luc-Decoy-15a/16 delivery increased Tie2 levels in ischemic skeletal muscle and improved post-LI angiogenesis and perfusion recovery, with reduced toe necrosis. Bioluminescent imaging (in vivo imaging system [IVIS]) provided evidence that the Ad.Luc-Decoy-15a/16 system responds to miR-15a/16 increases. In conclusion, we have provided novel mechanistic evidence of the therapeutic potential of local miR-15a/16 inhibition in LI.
AU  - Besnier,M
AU  - Shantikumar,S
AU  - Anwar,M
AU  - Dixit,P
AU  - Chamorro-Jorganes,A
AU  - Sweaad,W
AU  - Sala-Newby,G
AU  - Madeddu,P
AU  - Thomas,AC
AU  - Howard,L
AU  - Mushtaq,S
AU  - Petretto,E
AU  - Caporali,A
AU  - Emanueli,C
DO  - 10.1016/j.omtn.2019.05.002
EP  - 62
PY  - 2019///
SN  - 2162-2531
SP  - 49
TI  - miR-15a/-16 inhibit angiogenesis by targeting the Tie2 coding sequence: Therapeutic potential of a miR-15a/16 decoy system in limb ischemia.
T2  - Molecular Therapy : Nucleic Acids
UR  - http://dx.doi.org/10.1016/j.omtn.2019.05.002
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31220779
UR  - https://www.sciencedirect.com/science/article/pii/S2162253119301234?via%3Dihub
UR  - http://hdl.handle.net/10044/1/71795
VL  - 17
ER  -
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