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

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

doi:10.1096/fj.12-215533

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

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

Research output: Contribution to journal › Article › peer-review

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 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

Original language	English
Pages (from-to)	3938-3946
Number of pages	8
Journal	Faseb Journal
Volume	27
Issue number	10
DOIs	https://doi.org/10.1096/fj.12-215533
Publication status	Published - 1 Oct 2013

Keywords

15-HETE
COX-2 biomarker
Nonsteroidal anti-inflammatory drugs
Vascular inflammation

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10.1096/fj.12-215533

http://www.fasebj.org/content/27/10/3938.full.pdf+html

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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. (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. https://doi.org/10.1096/fj.12-215533

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title = "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",

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 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",

keywords = "15-HETE, COX-2 biomarker, Nonsteroidal anti-inflammatory drugs, Vascular inflammation",

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

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doi = "10.1096/fj.12-215533",

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Kirkby, NS, Chan, MV, Lundberg, MH, Massey, KA, Edmands, WMB, Mackenzie, LS, Holmes, E, Nicolaou, A, Warner, TD & 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, vol. 27, no. 10, pp. 3938-3946. https://doi.org/10.1096/fj.12-215533

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T1 - 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

AU - Kirkby, Nicholas S.

AU - Chan, Melissa V.

AU - Lundberg, Martina H.

AU - Massey, Karen A.

AU - Edmands, William M B

AU - Mackenzie, Louise S.

AU - Holmes, Elaine

AU - Nicolaou, Anna

AU - Warner, Timothy D.

AU - Mitchell, Jane A.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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 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

AB - 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 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

KW - 15-HETE

KW - COX-2 biomarker

KW - Nonsteroidal anti-inflammatory drugs

KW - Vascular inflammation

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DO - 10.1096/fj.12-215533

M3 - Article

C2 - 23792301

SN - 0892-6638

VL - 27

SP - 3938

EP - 3946

JO - Faseb Journal

JF - Faseb Journal

IS - 10

ER -

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

Abstract

Keywords

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