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Cyclooxygenase-1, not cydooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 10/23/2012, Vol. 109 Issue 43, p17597-17602, 6p
- Publication Year :
- 2012
-
Abstract
- Prostacyclin is an antithrombotic hormone produced by the endo-thelium, whose production is dependent on cydooxygenase (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 physio-logical 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 circula-tion. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 109
- Issue :
- 43
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 82930952
- Full Text :
- https://doi.org/10.1073/pnas.1209192109