TY - JOUR
T1 - Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis
AU - Spanbroek, Rainer
AU - Gräbner, Rolf
AU - Lötzer, Katharina
AU - Hildner, Markus
AU - Urbach, Anja
AU - Rühling, Katharina
AU - Moos, Michael P.W.
AU - Kaiser, Brigitte
AU - Cohnert, Tina U.
AU - Wahlers, Thorsten
AU - Zieske, Arthur
AU - Plenz, Gabriele
AU - Robenek, Horst
AU - Salbach, Peter
AU - Kühn, Hartmut
AU - Rådmark, Olof
AU - Samuelsson, Bengt
AU - Habenicht, Andreas J.R.
PY - 2003/2/4
Y1 - 2003/2/4
N2 - 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.
AB - 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.
KW - Arachidonic acid cascade
KW - Coronary heart disease
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U2 - 10.1073/pnas.242716099
DO - 10.1073/pnas.242716099
M3 - Article
C2 - 12552108
AN - SCOPUS:0037417973
SN - 0027-8424
VL - 100
SP - 1238
EP - 1243
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -