dc.contributor.author | Kirkby, N.S. | |
dc.contributor.author | Lundberg, M.H. | |
dc.contributor.author | Harrington, L.S. | |
dc.contributor.author | Leadbeater, P.D.M. | |
dc.contributor.author | Potter, C.M.F. | |
dc.contributor.author | Al-Yamani, M. | |
dc.contributor.author | Adeyemi, O. | |
dc.contributor.author | Mitchell, J.A. | |
dc.contributor.author | Warner, T.D. | |
dc.contributor.author | Milne, G.L. | |
dc.date.accessioned | 2013-04-29T09:10:00Z | |
dc.date.available | 2013-04-29T09:10:00Z | |
dc.date.issued | 2012-10-23 | |
dc.identifier.citation | Kirkby , N S , Lundberg , M H , Harrington , L S , Leadbeater , P D M , Potter , C M F , Al-Yamani , M , Adeyemi , O , Mitchell , J A , Warner , T D & Milne , G L 2012 , ' Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 109 , no. 43 , pp. 17597-17602 . https://doi.org/10.1073/pnas.1209192109 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.uri | http://hdl.handle.net/2299/10585 | |
dc.description | MEDLINE® is the source for the MeSH terms of this document. | |
dc.description.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. | en |
dc.format.extent | 6 | |
dc.format.extent | 487900 | |
dc.language.iso | eng | |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | |
dc.title | Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Department of Human and Environmental Sciences | |
dc.contributor.institution | Pharmacology and Clinical Science Research | |
dc.contributor.institution | Agriculture, Food and Veterinary Sciences | |
dc.contributor.institution | Cardiovascular Pathologies | |
dc.contributor.institution | Diabetic neuropathies | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1073/pnas.1209192109 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |