Imperial College London
Alternate

DrStephenWort

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Pulmonary Hypertension)
 
 
 
//

Contact

 

+44 (0)20 7351 8528s.wort

 
 
//

Location

 

305Sydney StreetRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Mumby:2021:10.1177/2045894021996190,
author = {Mumby, S and Perros, F and Hui, C and Xu, B and Xu, W and Elyasigomari, V and Hautefort, A and Manaud, G and Humbert, M and Chung, KF and Wort, SJ and Adcock, I},
doi = {10.1177/2045894021996190},
journal = {Pulmonary Circulation},
pages = {1--16},
title = {Extracellular matrix degradation pathways and fatty acid metabolism regulate distinct pulmonary vascular cell types in Pulmonary Arterial Hypertension},
url = {http://dx.doi.org/10.1177/2045894021996190},
volume = {11},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary arterial hypertension (PAH) describes a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling in the pre-capillary resistance arterioles. Left untreated, patients die from right heart failure. Pulmonary vascular remodelling involves all cell types but to date the precise roles of the different cells is unknown. This study investigated differences in basal gene expression between PAH and controls using both human pulmonary microvascular endothelial (HPMEC) and pulmonary artery smooth muscle cells (HPASMC). HPMEC and HPASMC from PAH patients and controls were cultured to confluence, harvested and RNA extracted. Whole genome sequencing was performed and after transcript quantification and normalization, we examined differentially expressed genes (DEGs) and applied gene set enrichment analysis (GSEA) to the DEGs to identify putative activated pathways.HPMEC displayed 1008 significant (p≤0.0001) DEGs in PAH samples compared to controls. In HPASMC there were 229 significant (p≤0.0001) DEGs between PAH and controls. Pathway analysis revealed distinctive differences: HPMEC display down-regulation of extracellular matrix organisation, collagen formation and biosynthesis, focal- and cell- adhesion molecules suggesting severe endothelial barrier dysfunction and vascular permeability in PAH pathogenesis. In contrast pathways in HPASMC were mainly up-regulated, including those for fatty acid metabolism, biosynthesis of unsaturated fatty acids, cell-cell and adherens junction interactions suggesting a more energy-driven proliferative phenotype. This suggests that the two cell types play different mechanistic roles in PAH pathogenesis and further studies are required to fully elucidate the role each plays and the interactions between these cell types in vascular remodelling in disease progression.
AU  - Mumby,S
AU  - Perros,F
AU  - Hui,C
AU  - Xu,B
AU  - Xu,W
AU  - Elyasigomari,V
AU  - Hautefort,A
AU  - Manaud,G
AU  - Humbert,M
AU  - Chung,KF
AU  - Wort,SJ
AU  - Adcock,I
DO  - 10.1177/2045894021996190
EP  - 16
PY  - 2021///
SN  - 2045-8940
SP  - 1
TI  - Extracellular matrix degradation pathways and fatty acid metabolism regulate distinct pulmonary vascular cell types in Pulmonary Arterial Hypertension
T2  - Pulmonary Circulation
UR  - http://dx.doi.org/10.1177/2045894021996190
UR  - https://journals.sagepub.com/doi/10.1177/2045894021996190
UR  - http://hdl.handle.net/10044/1/85866
VL  - 11
ER  -
Download