Imperial College London
Portrait Picture

DrChristopherRhodes

Faculty of Medicine, National Heart & Lung Institute

Reader in Pulmonary Vascular Disease
 
 
 
//

Contact

 

+44 (0)20 7594 7638c.rhodes07

 
 
//

Location

 

535ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Sindi:2020:10.1038/s41467-020-14966-x,
author = {Sindi, H and Russomanno, G and Satta, S and Abdul, Saalam V and Kyeong, Beom J and Qazi-Chaudhry, B and Ainscough, A and Szulcek, R and Bogaard, HJ and Morgan, C and Pullamsetti, S and Alzaydi, M and Rhodes, C and Piva, R and Eichstaedt, C and Grünig, E and Wilkins, M and Wojciak-Stothard, B},
doi = {10.1038/s41467-020-14966-x},
journal = {Nature Communications},
title = {Therapeutic potential of KLF2 induced exosomal microRNAs in pulmonary hypertension},
url = {http://dx.doi.org/10.1038/s41467-020-14966-x},
volume = {11},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodeling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice.This study shows that reduced  KLF2 signaling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling.
AU  - Sindi,H
AU  - Russomanno,G
AU  - Satta,S
AU  - Abdul,Saalam V
AU  - Kyeong,Beom J
AU  - Qazi-Chaudhry,B
AU  - Ainscough,A
AU  - Szulcek,R
AU  - Bogaard,HJ
AU  - Morgan,C
AU  - Pullamsetti,S
AU  - Alzaydi,M
AU  - Rhodes,C
AU  - Piva,R
AU  - Eichstaedt,C
AU  - Grünig,E
AU  - Wilkins,M
AU  - Wojciak-Stothard,B
DO  - 10.1038/s41467-020-14966-x
PY  - 2020///
SN  - 2041-1723
TI  - Therapeutic potential of KLF2 induced exosomal microRNAs in pulmonary hypertension
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-14966-x
UR  - http://hdl.handle.net/10044/1/77873
VL  - 11
ER  -
Download