Oxidation of
lipoproteins, particularly
low-density lipoprotein, is thought to play a major role in the development of
atherosclerosis. We set out to identify and quantitate the major
fatty acid oxidation products in human
atherosclerotic plaque obtained from individuals undergoing
carotid endarterectomy. Oxidized
lipids were extracted from plaque homogenate under conditions to prevent artifactual oxidation. Identification and quantitation was performed using HPLC and GC-MS. High levels of hydroxyoctadecanoic
acids (0.51 +/- 0.17 ng/microg of
linoleic acid), 15-hydroxyeicosatetranoic
acid (
HETE) (0.66 +/- 0.24 ng/microg of
arachidonic acid), and
11-HETE (0.84 +/- 0.24 ng/microg of
arachidonic acid) were detected in all
atherosclerotic plaques (n = 10). Low levels of 9-oxo-octadecanoic
acid (oxoODE) (0.04 +/- 0.01 ng/microg of
linoleic acid), were present in all samples, while 13-oxoODE (0.01 +/- 0.008 ng/microg of
linoleic acid) was present in only 4 of the 10 plaque samples. Of interest was the identification of two previously unidentified compounds in
atherosclerotic plaque, 11-oxo-eicosatetranoic
acid in 9 of the 10 samples and 5,6-dihydroxyeicosatetranoic
acid in 3 samples. Chiral analysis revealed that all the major compounds identified in this study are of a nonenzymatic origin. This study is the first to provide a convenient HPLC method to quantify all the products of both
linoleic acid and
arachidonic acid oxidation in human
atherosclerotic plaque. The quantitation of lipid peroxidation products in plaque may be important given the potential
biological activity of these compounds and their possible relationship to plaque pathogenesis and instability.