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.

Published

Journal Article

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 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. CONCLUSIONS: 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.

Full Text

Duke Authors

Cited Authors

  • Tsimikas, S; Aikawa, M; Miller, FJ; Miller, ER; Torzewski, M; Lentz, SR; Bergmark, C; Heistad, DD; Libby, P; Witztum, JL

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 27 / 1

Start / End Page

  • 175 - 181

PubMed ID

  • 17082490

Pubmed Central ID

  • 17082490

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

Digital Object Identifier (DOI)

  • 10.1161/01.ATV.0000251501.86410.03

Language

  • eng

Conference Location

  • United States