© 1997 American Heart Association, Inc.
Articles |
Prostaglandin F2-Like Compounds, F2-Isoprostanes, Are Present in Increased Amounts in Human Atherosclerotic Lesions
From the Institute of Biochemistry, University Clinics Charité, Humboldt University, Hessische Str 3–4, D-10115 Berlin, F.R. Germany (C.G., J.D.M., H.K.), and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tenn (L.J.R.).
Correspondence to Dr Hartmut Kühn, Institute for Biochemistry, University Clinics (Charité), Humboldt University, Hessische Str. 3–4, 10115 Berlin, F.R. Germany. E-mail hartmut.kuehn{at}rz.hu-berlin.de
Abstract Oxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1±21.2 pg/mg wet weight (n=10), which corresponds to 75.9±59.3 pg/mg dry weight. n contrast, human umbilical veins (n=10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4±0.7 pg/mg wet weight, which corresponds to 11.7±6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected.
These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.
Key Words: atherogenesis • hydroxy fatty acids • lipid peroxidation • LDL modification • cholesterol esters
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