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dc.contributor.authorKirkby, N.S.*
dc.contributor.authorChan, M.V.*
dc.contributor.authorLundberg, M.H.*
dc.contributor.authorMassey, Karen A.*
dc.contributor.authorEdmands, W.M.B.*
dc.contributor.authorMacKenzie, L.S.*
dc.contributor.authorHomes, E.*
dc.contributor.authorNicolaou, Anna*
dc.contributor.authorWarner, T.D.*
dc.contributor.authorMitchell, J.A.*
dc.date.accessioned2015-06-15T14:13:33Z
dc.date.available2015-06-15T14:13:33Z
dc.date.issued2013-10-21
dc.identifier.citationKirkby NS, Chan MV, Lundberg MH, Massey KA, Edmands WM, Mackenzie LS, Holmes E, Nicolaou A, Warner TD and Mitchell JA (2013) Aspirin-triggered 15-epi-lipoxin A4 predicts cyclooxygenase-2 in the lungs of LPS-treated mice but not in the circulation: implications for a clinical test. FASEB Journal 27 (10): 3938-3946.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7247
dc.description.abstractInhibition of cyclooxygenase (COX)-2 increases cardiovascular deaths. Identifying a biomarker of COX-2 is desirable but difficult, since COX-1 and COX-2 ordinarily catalyze formation of an identical product, prostaglandin H2. When acetylated by aspirin, however, COX-2 (but not COX-1) can form 15(R)-HETE, which is metabolized to aspirin-triggered lipoxin (ATL), 15-epi-lipoxin A4. Here we have used COX-1- and COX-2-knockout mice to establish whether plasma ATL could be used as a biomarker of vascular COX-2 in vivo. Vascular COX-2 was low but increased by LPS (10 mg/kg; i.p). Aspirin (10 mg/kg; i.v.) inhibited COX-1, measured as blood thromboxane and COX-2, measured as lung PGE2. Aspirin also increased the levels of ATL in the lungs of LPS-treated wild-type C57Bl6 mice (vehicle: 25.5±9.3 ng/ml; 100 mg/kg: 112.0±7.4 ng/ml; P<0.05). Despite this, ATL was unchanged in plasma after LPS and aspirin. This was true in wild-type as well as COX-1−/− and COX-2−/− mice. Thus, in mice in which COX-2 has been induced by LPS treatment, aspirin triggers detectable 15-epi-lipoxin A4 in lung tissue, but not in plasma. This important study is the first to demonstrate that while ATL can be measured in tissue, plasma ATL is not a biomarker of vascular COX-2 expression.—Kirkby, N. S., Chan, M. V., Lundberg, M. H., Massey, K. A., Edmands, W. M. B., MacKenzie, L. S., Holmes, E., Nicolaou, A., Warner, T. D., Mitchell, J. A. Aspirin-triggered 15-epi-lipoxin A4 predicts cyclooxygenase-2 in the lungs of LPS-treated mice but not in the circulation: implications for a clinical test.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1096/fj.12-215533en_US
dc.subject15-HETE; COX-2 biomarker; Vascular inflammation; Nonsteroidal anti-inflammatory drugs; Aspirin-triggered 15-epi-lipoxin A4;en_US
dc.titleAspirin-triggered 15-epi-lipoxin A4 predicts cyclooxygenase-2 in the lungs of LPS-treated mice but not in the circulation: implications for a clinical test.en_US
dc.status.refereedyesen_US
dc.typeArticleen_US
dc.type.versionNo full-text available in the repositoryen_US


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