Imperial College London
Portrait Picture

Professor Martin Wilkins

Faculty of Medicine, National Heart & Lung Institute

Professor of Clinical Pharmacology
 
 
 
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Contact

 

+44 (0)20 3313 6101m.wilkins Website

 
 
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Assistant

 

Mrs Elizabeth O'Brien +44 (0)20 3313 6101

 
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Location

 

NIHR Imperial Clinical Research FacilityICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Russomanno:2021:10.1016/j.omtn.2020.10.042,
author = {Russomanno, G and Jo, KB and Abdul-Salam, V and Morgan, C and Endruschat, J and Schaeper, U and Osman, A and Alzaydi, M and Wilkins, M and Wojciak-Stothard, B},
doi = {10.1016/j.omtn.2020.10.042},
journal = {Molecular Therapy : Nucleic Acids},
pages = {142--153},
title = {miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1016/j.omtn.2020.10.042},
volume = {23},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Circulating levels of endothelial miR-150 are reduced in pulmonary arterial hypertension (PAH) and act as an independent predictor of patient survival, but links between endothelial miR-150 and vascular dysfunction are not well understood. We studied the effects of endothelial miR-150 supplementation and inhibition in PAH mice and cells from patients with idiopathic PAH. The role of selected mediators of miR-150 identified by RNA sequencing was evaluated in vitro and in vivo. Endothelium-targeted miR-150 delivery prevented the disease in Sugen/hypoxia mice, while endothelial knockdown of miR-150 had adverse effects. miR-150 target genes revealed significant associations with PAH pathways, including proliferation, inflammation, and phospholipid signaling, with PTEN-like mitochondrial phosphatase (PTPMT1) most markedly altered. PTPMT1 reduced inflammation and apoptosis and improved mitochondrial function in human pulmonary endothelial cells and blood-derived endothelial colony-forming cells from idiopathic PAH. Beneficial effects of miR-150 in vitro and in vivo were linked with PTPMT1-dependent biosynthesis of mitochondrial phospholipid cardiolipin and reduced expression of pro-apoptotic, pro-inflammatory, and pro-fibrotic genes, including c-MYB, NOTCH3, transforming growth factor β (TGF-β), and Col1a1. In conclusion, we are the first to show that miR-150 supplementation attenuates pulmonary endothelial damage induced by vascular stresses and may be considered as a potential therapeutic strategy in PAH.
AU  - Russomanno,G
AU  - Jo,KB
AU  - Abdul-Salam,V
AU  - Morgan,C
AU  - Endruschat,J
AU  - Schaeper,U
AU  - Osman,A
AU  - Alzaydi,M
AU  - Wilkins,M
AU  - Wojciak-Stothard,B
DO  - 10.1016/j.omtn.2020.10.042
EP  - 153
PY  - 2021///
SN  - 2162-2531
SP  - 142
TI  - miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension
T2  - Molecular Therapy : Nucleic Acids
UR  - http://dx.doi.org/10.1016/j.omtn.2020.10.042
UR  - http://hdl.handle.net/10044/1/85107
VL  - 23
ER  -
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