title: Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis.
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, 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.
authors.affiliation: Institute for Vascular Medicine, Friedrich-Schiller-University of Jena, Nordhäuserstrasse 78, 99089 Erfurt, Germany. spanbroek@zmkh.ef.uni-jena.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanbroek
authors.forename: Rolf
authors.initials: R
authors.lastname: Grabner
authors.forename: Katharina
authors.initials: K
authors.lastname: Lotzer
authors.forename: Markus
authors.initials: M
authors.lastname: Hildner
authors.forename: Anja
authors.initials: A
authors.lastname: Urbach
authors.forename: Katharina
authors.initials: K
authors.lastname: Ruhling
authors.forename: Michael P W
authors.initials: MP
authors.lastname: Moos
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kaiser
authors.forename: Tina U
authors.initials: TU
authors.lastname: Cohnert
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.forename: Arthur
authors.initials: A
authors.lastname: Zieske
authors.forename: Gabriele
authors.initials: G
authors.lastname: Plenz
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Peter
authors.initials: P
authors.lastname: Salbach
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuhn
authors.forename: Olof
authors.initials: O
authors.lastname: Radmark
authors.forename: Bengt
authors.initials: B
authors.lastname: Samuelsson
authors.forename: Andreas J R
authors.initials: AJ
authors.lastname: Habenicht
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001011:Aorta / Q000201:enzymology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis / Q000378:metabolism*; D001158:Arteries / Q000201:enzymology*; D001161:Arteriosclerosis / Q000473:pathology; D019070:Cell Lineage; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D012313:RNA; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule