1. Cyclooxygenase-1, not cydooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system.
- Author
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Kirkby, Nicholas S., Lundberg, Martina H., Harrington, Louise S., Leadbeater, Philip D. M., Milne, Ginger L., Potter, Claire M. F., Al-Yamani, Malak, Adeyemi, Oladipupo, Warner, Timothy D., and Mitchell, Jane A.
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CYCLOOXYGENASES ,PROSTACYCLIN ,CARDIOVASCULAR system physiology ,ANTICOAGULANTS ,CARDIOTOXICITY ,METABOLITES - 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]
- Published
- 2012
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