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Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17597-602. doi: 10.1073/pnas.1209192109. Epub 2012 Oct 8.

Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system.

Author information

1
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.

Erratum in

  • Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1561.

Abstract

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.

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PMID:
23045674
PMCID:
PMC3491520
DOI:
10.1073/pnas.1209192109
[Indexed for MEDLINE]
Free PMC Article

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