title: Disease stage-dependent accumulation of lipid and protein oxidation products in human atherosclerosis.
abstract: Oxidative modification of low-density lipoprotein is thought to promote arterial lipid accumulation and atherogenesis. Previous studies reported on the presence of certain lipid or protein oxidation products in lesions, although a systematic investigation measuring several oxidation parameters and the accumulation of nonoxidized lipids and antioxidants at various stages of atherosclerosis has not been performed in the same tissue. Using the intimal lipoprotein-containing fraction of human aortic lesions, we demonstrate here that cholesterol accumulated with lesion development and that this increase was already significant at the fatty streak stage. By comparison, cholesterylesters increased significantly only in fibro-fatty and more complex lesions that also contained significantly increased amounts of cholesterylester hydro(pero)xides and 27-hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation product detected. Despite accumulation of oxidized lipid, alpha-tocopherol was also present and maintained at a comparable level over the disease process. Of the oxidized protein moieties measured only o,o-dityrosine increased with disease, although chlorotyrosines were present at relatively high levels in all lesions compared to healthy vessels. Our data show that accumulation of nonoxidized lipid precedes that of oxidized lipid in human aortic lesions.
authors.affiliation: Department of Biochemistry, Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, NSW 2050, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Upston
authors.forename: Xianwa
authors.initials: X
authors.lastname: Niu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mashima
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Revathy
authors.initials: R
authors.lastname: Senthilmohan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.forename: Roger T
authors.initials: RT
authors.lastname: Dean
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D050356:Lipid Metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002788:Cholesterol Esters; D011506:Proteins; D014443:Tyrosine; D010649:Phenylalanine; D002784:Cholesterol