Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis

Rainer Spanbroek, Rolf Gräbner, Katharina Lötzer, Markus Hildner, Anja Urbach, Katharina Rühling, Michael P.W. Moos, Brigitte Kaiser, Tina U. Cohnert, Thorsten Wahlers, Arthur Zieske, Gabriele Plenz, Horst Robenek, Peter Salbach, Hartmut Kühn, Olof Rådmark, Bengt Samuelsson, Andreas J.R. Habenicht

Research output: Contribution to journalArticle

399 Scopus citations

Abstract

Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocytetype 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.

Original languageEnglish (US)
Pages (from-to)1238-1243
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number3
DOIs
StatePublished - Feb 4 2003

Keywords

  • Arachidonic acid cascade
  • Coronary heart disease

ASJC Scopus subject areas

  • General

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