Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1616-1624
© 1995 American Heart Association, Inc.
Articles |
Human Atherosclerotic Plaque Contains Both Oxidized Lipids and Relatively Large Amounts of 
-Tocopherol and Ascorbate
From the Biochemistry (C.S., R.S.) and Cell Biology (R.T.D.) Groups, The Heart Research Institute, and the Department of Vascular Surgery (J.M.), Royal Prince Alfred Hospital, Camperdown, Australia.
Correspondence to Dr Roland Stocker, The Heart Research Institute, 145 Missenden Rd, Camperdown, NSW 2050, Australia.
Abstract We assessed the antioxidant status and contents of
unoxidized and oxidized lipids in freshly obtained,
homogenized samples of both normal human iliac arteries and
carotid and femoral atherosclerotic plaque. Optimal sample preparation
involved homogenization of human atherosclerotic
plaque for 5 minutes, which resulted in recovery of most of the
unoxidized and oxidized lipids without substantial destruction of
endogenous vitamins C and E and 87% and 43% recoveries of
added standards of 
-tocotrienol and isoascorbate, respectively.
The total protein, lipid, and antioxidant levels obtained from human
plaque varied among donors, although the reproducibility of replicates
from a single sample was within 3%, except for ubiquinone-10 and
ascorbate, which varied by 20% and 25%, respectively. Plaque samples
contained significantly more ascorbate and urate than control arteries,
with no discernible difference in the vitamin C redox status between
plaque and control materials. The concentrations of
-tocopherol and ubiquinone-10 were comparable in
plaque samples and control arteries. However, approximately 9 mol
percent of plaque -tocopherol was present as
-tocopherylquinone, whereas this oxidation product of
vitamin E was not detectable in control arteries. Coenzyme
Q10 in plaque and control arteries was only detected in the
oxidized form ubiquinone-10, although coenzyme Q10
oxidation may have occurred during processing. The most abundant of all
studied lipids in plaque samples was free cholesterol,
followed by cholesteryl oleate and cholesteryl linoleate (Ch18:2).
Approximately 30% of plaque Ch18:2 was oxidized, with 17%, 12%,
and 1% present as fatty acyl hydroxides, ketones, and
hydroperoxides, respectively. In comparison,
7-ketocholesterol was detected at an 
75-fold lower
concentration. Normal arteries contained similar levels of protein as
atherosclerotic arteries, much less free cholesterol, and
no detectable amounts of unoxidized or oxidized cholesteryl esters.
Together, these results demonstrate the coexistence in human plaque of
large amounts of oxidized cholesteryl esters with significant
concentrations of ascorbate and vitamin E in their reduced,
antioxidant-active form. We conclude that compared with healthy
human arteries, advanced atherosclerotic plaques are not deficient in
the antioxidant vitamins C and E, despite the occurrence of massive
lipid oxidation.
Key Words: antioxidants • atherosclerosis • oxidative stress • 7-ketocholesterol • vitamin E
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