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

Kirkby NS, Lundberg MH, Harrington LS, Leadbeater PD, Milne GL, Potter CM, Al-Yamani M, Adeyemi O, Warner TD, Mitchell JA
Proc Natl Acad Sci U S A. 2012 109 (43): 17597-602

PMID: 23045674 · PMCID: PMC3491520 · DOI:10.1073/pnas.1209192109

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.

MeSH Terms (13)

Animals Blotting, Western Cardiovascular System Cells, Cultured Cyclooxygenase 1 Cyclooxygenase 2 Endothelium, Vascular Epoprostenol Humans Immunohistochemistry Mice Mice, Inbred C57BL Mice, Knockout

Connections (2)

This publication is referenced by other Labnodes entities:

Links