title: Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein.
abstract: Oxidized low density lipoprotein (LDL) possesses several atherogenic properties. The mechanisms by which LDL becomes oxidized in vivo remain unknown, but previous studies have suggested that 15-lipoxygenase may be one of the factors involved in the initiation of LDL oxidation in the arterial wall. 3 wk after a retrovirus-mediated 15-lipoxygenase gene transfer into iliac arteries of normocholesterolemic rabbits there was a threefold increase in 15-lipoxygenase activity but no signs of LDL oxidation. However, when animals were made moderately hypercholesterolemic by feeding a 0.13% cholesterol diet for 2-3 wk starting from day 4 after the gene transfer, oxidation-specific lipid-protein adducts characteristic of oxidized LDL were detected in 15-lipoxygenase-transduced arteries. Control experiments in which contralateral iliac arteries were transduced with beta-galactosidase-containing retroviruses showed only occasional signs of the presence of oxidation-specific adducts. The results support the hypothesis that products derived from the 15-lipoxygenase activity are involved in the induction of LDL oxidation within the arterial wall, provided that sufficient concentrations of lipoproteins are present in the artery.
authors.affiliation: A. I. Virtanen Institute, University of Kuopio, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: J
authors.initials: J
authors.lastname: Luoma
authors.forename: H
authors.initials: H
authors.lastname: Viita
authors.forename: T
authors.initials: T
authors.lastname: Hiltunen
authors.forename: T
authors.initials: T
authors.lastname: Sisto
authors.forename: T
authors.initials: T
authors.lastname: Nikkari
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001158:Arteries / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D017539:Tunica Intima / Q000166:cytology
chemical_list: D008077:Lipoproteins, LDL; D001093:Arachidonate 15-Lipoxygenase