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Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2002-01-0316. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0316v1 100/4/1340    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sethi, S. Articles by Mayadas, T. N. Search for Related Content PubMed PubMed Citation Articles by Sethi, S. Articles by Mayadas, T. N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2002, Vol. 100, No. 4, pp. 1340-1346 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR Sanjeev Sethi, Ouliana Ziouzenkova, Heyu Ni, Denisa D. Wagner, Jorge Plutzky, and Tanya N. Mayadas From the Vascular Research Division, Department of Pathology, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA. Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor  (PPAR), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)-treated mice. This occurred via a PPAR-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPAR-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPAR-mediated anti-inflammatory effect of oxidized EPA. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-H. Chen, T.-W. Chen, and H. Lin Prostacyclin-induced peroxisome proliferator-activated receptor-{alpha} translocation attenuates NF-{kappa}B and TNF-{alpha} activation after renal ischemia-reperfusion injury Am J Physiol Renal Physiol, October 1, 2009; 297(4): F1109 - F1118. [Abstract] [Full Text] [PDF] M. K. Duda, K. M. O'Shea, and W. C. Stanley {omega}-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential Cardiovasc Res, October 1, 2009; 84(1): 33 - 41. [Abstract] [Full Text] [PDF] H. Yamada, M. Yoshida, Y. Nakano, T. Suganami, N. Satoh, T. Mita, K. Azuma, M. Itoh, Y. Yamamoto, Y. Kamei, et al. 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