on November 2, 2006
Published online before print November 2, 2006, doi: 10.1161/01.ATV.0000251501.86410.03
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Submitted on June 12, 2006
Accepted on October 11, 2006
Increased Plasma Oxidized Phospholipid:Apolipoprotein B-100 Ratio With Concomitant Depletion of Oxidized Phospholipids From Atherosclerotic Lesions After Dietary Lipid-Lowering. A Potential Biomarker of Early Atherosclerosis Regression
Sotirios Tsimikas *;
From Divisions of Cardiovascular Diseases (S.T.) and Endocrinology and Metabolism (E.R.M., J.L.W.), Department of Medicine, University of California San Diego, Calif; Cardiovascular Division (M.A., P.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Institute of Clinical Chemistry and Laboratory Medicine (M.T.), Johannes Gutenberg University, Mainz, Germany; Department of Vascular Surgery (C.B.), Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Division of Cardiovascular Diseases (F.M., S.L., D.D.H.), Veterans Affairs Medical Center and Carver College of Medicine, University of Iowa, Iowa City, Iowa.
* To whom correspondence should be addressed. E-mail: stsimikas{at}ucsd.edu.
Background--Oxidized phospholipids (OxPL) are pro-inflammatory. We evaluated whether changes in plasma levels of OxPL associated with apolipoprotein B-100 (apoB-100) reflect changes in OxPL content in atherosclerotic plaques during dietary-induced atherosclerosis progression and regression.
Methods and Results--OxPL content was measured in plasma and immunohistochemically in aortic plaques with antibody E06 in cynomolgus monkeys and New Zealand White rabbits at baseline, after a high-fat/high-cholesterol diet and after reversion to normal chow. The OxPL/apoB ratio, representing the content of OxPL on individual apoB-100 particles, and total apoB-OxPL (OxPL/apoB multiplied by plasma apoB levels), reflecting the OxPL content on all apoB-100 particles, were measured. Total apoB-OxPL plasma levels increased 3-fold (P<0.0001) during hypercholesterolemia and decreased 
75% (P<0.0001) during reversion to normocholesterolemia. In contrast, OxPL/apoB levels decreased significantly (P<0.0001) during hypercholesterolemia and increased significantly (P=0.0002) during reversion to normocholesterolemia. Immunostaining revealed that during atherosclerosis progression OxPL co-localized with apoB-100, whereas during regression OxPL virtually disappeared.
Conclusion--In the setting of overall reduction of plasma OxPL levels after dietary lipid-lowering, increases in the OxPL/apoB ratio reflect reduced content of OxPL in atherosclerotic plaques. These data suggest that changes in the OxPL/apoB ratio may reflect early atherosclerosis regression.
Key words: antibodies • atherosclerosis • lipoproteins • oxidation • phospholipids
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