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; Masanori Aikawa; Francis J Miller Jr; Elizabeth R Miller; Michael Torzewski; Steven R Lentz; Claes Bergmark; Donald D Heistad; Peter Libby; Joseph L Witztum

doi:10.1161/01.ATV.0000251501.86410.03

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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

Journal article

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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, Masanori Aikawa, Francis J Miller Jr, Elizabeth R Miller, Michael Torzewski, Steven R Lentz, Claes Bergmark, Donald D Heistad, Peter Libby and Joseph L Witztum

Arteriosclerosis, thrombosis, and vascular biology, Vol.27(1), pp.175-181

01/2007

DOI: 10.1161/01.ATV.0000251501.86410.03

PMID: 17082490

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Abstract

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. 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 approximately 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. 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.

Hypercholesterolemia - diet therapy

Predictive Value of Tests

Rabbits

Atherosclerosis - pathology

Hypercholesterolemia - blood

Oxidation-Reduction

Apolipoprotein B-100 - blood

Macaca fascicularis

Male

Carotid Stenosis - pathology

Carotid Stenosis - metabolism

Disease Progression

Contraindications

Atherosclerosis - blood

Animals

Hypercholesterolemia - pathology

Phospholipids - blood

Cholesterol, Dietary

Details

Title: Subtitle: 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
Creators: Sotirios Tsimikas - Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, USA. stsimikas@ucsd.edu
Masanori Aikawa
Francis J Miller Jr
Elizabeth R Miller
Michael Torzewski
Steven R Lentz
Claes Bergmark
Donald D Heistad
Peter Libby
Joseph L Witztum
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.27(1), pp.175-181
DOI: 10.1161/01.ATV.0000251501.86410.03
PMID: 17082490
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Publisher: United States
Grant note: HL-56985 / NHLBI NIH HHS HL-56989 / NHLBI NIH HHS R01 HL081750-02 / NHLBI NIH HHS R01 HL081750 / NHLBI NIH HHS HL63943 / NHLBI NIH HHS R01 HL081750-04 / NHLBI NIH HHS HL62984 / NHLBI NIH HHS R01 HL081750-01 / NHLBI NIH HHS R01 HL063943 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS R01 HL081750-03 / NHLBI NIH HHS
Language: English
Date published: 01/2007
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040259802771

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