Imperial College London
Alternate

DrNicholasKirkby

Faculty of Medicine, National Heart & Lung Institute

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3075n.kirkby

 
 
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Location

 

364Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mitchell:2021:10.1126/sciadv.abf6054,
author = {Mitchell, J and Shala, F and Lopes, Pires M and Loy, R and Ravendren, A and Benson, J and Urquhart, P and Nicolaou, A and Herschman, H and Kirkby, N},
doi = {10.1126/sciadv.abf6054},
journal = {Science Advances},
title = {Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation},
url = {http://dx.doi.org/10.1126/sciadv.abf6054},
volume = {7},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Endothelial cyclooxygenase-1–derived prostanoids, including prostacyclin, have clear cardioprotective roles associated with their anti-thrombotic potential but have also been suggested to have paradoxical pathological activities within arteries. To date it has not been possible to test the importance of this because no models have been available that separate vascular cyclooxygenase-1 products from those generated elsewhere. Here, we have used unique endothelial-specific cyclooxygenase-1 knockout mice to show that endothelial cyclooxygenase-1 produces both protective and pathological products. Functionally, however, the overall effect of these was to drive pathological responses in the context of both vasoconstriction in vitro and the development of atherosclerosis and vascular inflammation in vivo. These data provide the first demonstration of a pathological role for the vascular cyclooxygenase-1 pathway, highlighting its potential as a therapeutic target. They also emphasize that, across biology, the role of prostanoids is not always predictable due to unique balances of context, products, and receptors.
AU  - Mitchell,J
AU  - Shala,F
AU  - Lopes,Pires M
AU  - Loy,R
AU  - Ravendren,A
AU  - Benson,J
AU  - Urquhart,P
AU  - Nicolaou,A
AU  - Herschman,H
AU  - Kirkby,N
DO  - 10.1126/sciadv.abf6054
PY  - 2021///
SN  - 2375-2548
TI  - Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation
T2  - Science Advances
UR  - http://dx.doi.org/10.1126/sciadv.abf6054
UR  - http://hdl.handle.net/10044/1/87025
VL  - 7
ER  -
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