Imperial College London
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DrAndrewCowburn

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer (Non-Clinical)
 
 
 
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Contact

 

a.cowburn

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lambden:2021:10.1186/s40635-021-00390-y,
author = {Lambden, S and Cowburn, AS and Macias, D and Garrud, TAC and Krause, BJ and Giussani, DA and Summers, C and Johnson, RS},
doi = {10.1186/s40635-021-00390-y},
journal = {Intensive Care Medicine Experimental},
title = {Endothelial cell regulation of systemic haemodynamics and metabolism acts through the HIF transcription factors},
url = {http://dx.doi.org/10.1186/s40635-021-00390-y},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: The vascular endothelium has important endocrine and paracrine roles, particularly in the regulation of vascular tone and immune function, and it has been implicated in the pathophysiology of a range of cardiovascular and inflammatory conditions. This study uses a series of transgenic murine models to explore for the first time the role of the hypoxia-inducible factors, HIF-1α and HIF-2α in the pulmonary and systemic circulations as potential regulators of systemic vascular function in normoxic or hypoxic conditions and in response to inflammatory stress. We developed a series of transgenic mouse models, the HIF-1α Tie2Cre, deficient in HIF1-α in the systemic and pulmonary vascular endothelium and the L1Cre, a pulmonary endothelium specific knockout of HIF-1α or HIF-2α. In vivo, arterial blood pressure and metabolic activity were monitored continuously in normal atmospheric conditions and following an acute stimulus with hypoxia (10%) or lipopolysaccharide (LPS). Ex vivo, femoral artery reactivity was assessed using wire myography. Results: Under normoxia, the HIF-1α Tie2Cre mouse had increased systolic and diastolic arterial pressure compared to litter mate controls over the day–night cycle under normal environmental conditions. VO2 and VCO2 were also increased. Femoral arteries displayed impaired endothelial relaxation in response to acetylcholine mediated by a reduction in the nitric oxide dependent portion of the response. HIF-1α L1Cre mice displayed a similar pattern of increased systemic blood pressure, metabolic rate and impaired vascular relaxation without features of pulmonary hypertension, polycythaemia or renal dysfunction under normal conditions. In response to acute hypoxia, deficiency of HIF-1α was associated with faster resolution of hypoxia-induced haemodynamic and metabolic compromise. In addition, systemic haemodynamics were less compromised by LPS treatment. Conclusions: These
AU  - Lambden,S
AU  - Cowburn,AS
AU  - Macias,D
AU  - Garrud,TAC
AU  - Krause,BJ
AU  - Giussani,DA
AU  - Summers,C
AU  - Johnson,RS
DO  - 10.1186/s40635-021-00390-y
PY  - 2021///
TI  - Endothelial cell regulation of systemic haemodynamics and metabolism acts through the HIF transcription factors
T2  - Intensive Care Medicine Experimental
UR  - http://dx.doi.org/10.1186/s40635-021-00390-y
VL  - 9
ER  -
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