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
Bibliographical noteThis 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.
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