Document Detail

Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system.
MedLine Citation:
PMID:  23045674     Owner:  NLM     Status:  MEDLINE    
Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production and that this explains the cardiovascular toxicity associated with COX-2 inhibition, yet the evidence for this relies on indirect evidence from urinary metabolites. Here we have used a range of experimental approaches to explore which isoform drives the production of prostacyclin in vitro and in vivo. Our data show unequivocally that under physiological conditions it is COX-1 and not COX-2 that drives prostacyclin production in the cardiovascular system, and that urinary metabolites do not reflect prostacyclin production in the systemic circulation. With the idea that COX-2 in endothelium drives prostacyclin production in healthy individuals removed, we must seek new answers to why COX-2 inhibitors increase the risk of cardiovascular events to move forward with drug discovery and to enable more informed prescribing advice.
Nicholas S Kirkby; Martina H Lundberg; Louise S Harrington; Philip D M Leadbeater; Ginger L Milne; Claire M F Potter; Malak Al-Yamani; Oladipupo Adeyemi; Timothy D Warner; Jane A Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17597-602     Citation Subset:  IM    
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.
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MeSH Terms
Blotting, Western
Cardiovascular System / metabolism*
Cells, Cultured
Cyclooxygenase 1 / genetics,  metabolism*
Cyclooxygenase 2 / genetics,  metabolism*
Endothelium, Vascular / cytology,  enzymology,  metabolism
Epoprostenol / biosynthesis*
Mice, Inbred C57BL
Mice, Knockout
Grant Support
0852551Z108/Z//Wellcome Trust
Reg. No./Substance:
35121-78-9/Epoprostenol; EC 1; EC 2
Comment In:
Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E184   [PMID:  23437445 ]
Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E183   [PMID:  23292931 ]
Erratum In:
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1561

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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