Imperial College London
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Professor Beata Wojciak-Stothard

Faculty of Medicine, National Heart & Lung Institute

Professor in Vascular Biology
 
 
 
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Contact

 

+44 (0)20 7594 6821b.wojciak-stothard

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Aldabbous:2016:10.1161/ATVBAHA.116.307634,
author = {Aldabbous, L and Abdul-Salam, V and McKinnon, T and Duluc, L and Pepke-Zaba, J and Southwood, M and Ainscough, AJ and Hadinnapola, C and Wilkins, M and Toshner, M and Wojciak-Stothard, B},
doi = {10.1161/ATVBAHA.116.307634},
journal = {Arteriosclerosis, Thrombosis, and Vascular Biology},
pages = {2078--2087},
title = {Neutrophil Extracellular Traps Promote Angiogenesis: Evidence From Vascular Pathology in Pulmonary Hypertension.},
url = {http://dx.doi.org/10.1161/ATVBAHA.116.307634},
volume = {36},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVE: Inflammation and dysregulated angiogenesis are features of endothelial dysfunction in pulmonary hypertension. Neutrophil extracellular traps (NETs), produced by dying neutrophils, contribute to pathogenesis of numerous vascular disorders but their role in pulmonary hypertension has not been studied. We sought evidence of (NETs) formation in pulmonary hypertension and investigated the effect of NETs on endothelial function. APPROACH AND RESULTS: Plasma and lung tissues of patients with pulmonary hypertension were analyzed for NET markers. The effects of NETs on endothelial function were studied in vitro and in vivo. Patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary hypertension showed elevated plasma levels of DNA, neutrophil elastase, and myeloperoxidase. NET-forming neutrophils and extensive areas of NETosis were found in the occlusive plexiform lesions and vascularized intrapulmonary thrombi. NETs induced nuclear factor κB-dependent endothelial angiogenesis in vitro and increased vascularization of matrigel plugs in vivo. Angiogenic responses were associated with increased release of matrix metalloproteinase-9, heparin-binding EGF-like growth factor, latency-associated peptide of the transforming growth factor β1, and urokinase-type plasminogen activator, accompanied by increased endothelial permeability and cell motility. NETs-induced responses depended on myeloperoxidase/H2O2-dependent activation of Toll-like receptor 4/nuclear factor κB signaling. NETs stimulated the release of endothelin-1 in HPAECs and stimulated pulmonary smooth muscle cell proliferation in vitro. CONCLUSIONS: We are the first to implicate NETs in angiogenesis and provide a functional link between NETs and inflammatory angiogenesis in vitro and in vivo. We demonstrate the potential pathological relevance of this in 2 diseases of disordered vascular homeostasis, pulmonary arterial hypertension and chronic thromboembolic pulmonary
AU  - Aldabbous,L
AU  - Abdul-Salam,V
AU  - McKinnon,T
AU  - Duluc,L
AU  - Pepke-Zaba,J
AU  - Southwood,M
AU  - Ainscough,AJ
AU  - Hadinnapola,C
AU  - Wilkins,M
AU  - Toshner,M
AU  - Wojciak-Stothard,B
DO  - 10.1161/ATVBAHA.116.307634
EP  - 2087
PY  - 2016///
SN  - 1079-5642
SP  - 2078
TI  - Neutrophil Extracellular Traps Promote Angiogenesis: Evidence From Vascular Pathology in Pulmonary Hypertension.
T2  - Arteriosclerosis, Thrombosis, and Vascular Biology
UR  - http://dx.doi.org/10.1161/ATVBAHA.116.307634
UR  - http://hdl.handle.net/10044/1/39781
VL  - 36
ER  -
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