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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.
- Source :
- FASEB Journal; Oct2013, Vol. 27 Issue 10, p3938-3946, 9p
- Publication Year :
- 2013
-
Abstract
- Inhibition 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 H<subscript>2</subscript>. 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 A<subscript>4</subscript>. 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 PGE<subscript>2</subscript>. 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<superscript>-/-</superscript> and COX-2<superscript>-/-</superscript> mice. Thus, in mice in which COX-2 has been induced by LPS treatment, aspirin triggers detectable 15-epi-lipoxin A<subscript>4</subscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 27
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 91251369
- Full Text :
- https://doi.org/10.1096/fj.12-215533