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

  • Rainer Spanbroek
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Rolf Gräbner
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Katharina Lötzer
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Markus Hildner
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Anja Urbach
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Katharina Rühling
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Michael P. W. Moos
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Brigitte Kaiser
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Tina U. Cohnert
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Thorsten Wahlers
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Arthur Zieske
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Gabriele Plenz
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Horst Robenek
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Peter Salbach
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Hartmut Kühn
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Olof Rådmark
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Bengt Samuelsson
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...
  • Andreas J. R. Habenicht
    Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany; Department of Cardio-Thoracic and Vascular Surgery, Friedrich-Schiller-University of Jena, Bachstrasse 18, 07740 Jena, Germany; Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112-1393; Institute for Atherosclerosis Research, Domagkstrasse 3, 48149 Münster, Germany; Department of Medicine, Division of Cardiology, University of Heidelberg Medical...

説明

<jats:p>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, reticulocyte-type 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.</jats:p>

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