Aspirin triggered 15-epi-lipoxin A4 predicts cyclo-oxygenase-2 in the lungs of LPS treated mice but not in the circulation: implications for a clinical test

Nicholas S. Kirkby, Melissa Chan, Martina H. Lundberg, Karen A. Massey, William M.B. Edmands, Louise Mackenzie, Elaine Holmes, Anna Nicolaou, Timothy D. Warner, Jane Mitchell

Research output: Contribution to journalArticle

Abstract

Inhibition of cyclooxygenase (COX)-2increases cardiovascular deaths. Identifying a biomarkerof COX-2 is desirable but difficult, since COX-1and COX-2 ordinarily catalyze formation of an identicalproduct, 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 usedCOX-1- and COX-2-knockout mice to establish whetherplasma ATL could be used as a biomarker of vascularCOX-2 in vivo. Vascular COX-2 was low but increasedby LPS (10 mg/kg; i.p). Aspirin (10 mg/kg; i.v.) inhibitedCOX-1, measured as blood thromboxane andCOX-2, measured as lung PGE2. Aspirin also increasedthe levels of ATL in the lungs of LPS-treated wild-typeC57Bl6 mice (vehicle: 25.59.3 ng/ml; 100 mg/kg:112.07.4 ng/ml; P<0.05). Despite this, ATL wasunchanged in plasma after LPS and aspirin. This wastrue in wild-type as well as COX-1/ and COX-2/mice. Thus, in mice in which COX-2 has been inducedby LPS treatment, aspirin triggers detectable 15-epilipoxinA4 in lung tissue, but not in plasma. Thisimportant study is the first to demonstrate that whileATL can be measured in tissue, plasma ATL is not abiomarker 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. Aspirintriggered15-epi-lipoxin A4 predicts cyclooxygenase-2 inthe lungs of LPS-treated mice but not in the circulation:implications for a clinical test
Original languageEnglish
Pages (from-to)3938-3946
Number of pages9
JournalFaseb journal
Volume27
Issue number10
DOIs
Publication statusPublished - 1 Jun 2013

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This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) (http://creativecommons.org/licenses/by/3.0/deed.en_US) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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    Kirkby, N. S., Chan, M., Lundberg, M. H., Massey, K. A., Edmands, W. M. B., Mackenzie, L., Holmes, E., Nicolaou, A., Warner, T. D., & Mitchell, J. (2013). Aspirin triggered 15-epi-lipoxin A4 predicts cyclo-oxygenase-2 in the lungs of LPS treated mice but not in the circulation: implications for a clinical test. Faseb journal, 27(10), 3938-3946. https://doi.org/10.1096/fj.12-215533