University of Hertfordshire

From the same journal

From the same journal


  • 906541

    Final published version, 778 KB, PDF document

  • N.S. Kirkby
  • A.K. Zaiss
  • P. Urquhart
  • J. Jiao
  • P.J. Austin
  • Malak Al-Yamani
  • M.H. Lundberg
  • Louise MacKenzie
  • T.D. Warner
  • A. Nicolaou
  • H.R. Herschman
  • J.A. Mitchell
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Original languageEnglish
Article numbere69524
JournalPLoS ONE
Publication statusPublished - 9 Jul 2013


There are two schools of thought regarding the cyclooxygenase (COX) isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibodybased
techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the
circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter
mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed
substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the
thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system


This research was supported by a program grant from the Wellcome Trust (0852551Z108/Z to JAM) and NIH-NCI P50 award CA086306 (to HRH). Copyright: © 2013 Kirkby et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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