Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 20, Issue 3, Pages 689-697Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.20.3.689
Keywords
atherosclerosis; lipoproteins; oxidation; radioisotopes; imaging
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL056989] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-56989, HL-07444] Funding Source: Medline
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To determine whether labeled antibodies against oxidized LDL (OxLDL) offer advantages for quantifying atherosclerosis, we compared in vivo aortic uptake of I-125-labeled MDA2, a monoclonal antibody against malondialdehyde-lysine epitopes), atherosclerotic surface area, and aortic weight in Watanabe heritable hyperlipidemic and New Zealand White rabbits and in low density lipoprotein receptor-deficient (LDLR-/-) and apolipoprotein E-deficient (apoE(-/-)) mice. Absolute and specific uptakes of I-125-MDA2 were significantly greater in plaque than in normal aortas. Uptake of I-125-MDA2 significantly correlated with aortic weight and percent atherosclerotic surface area in rabbits and mice. To assess whether I-125-MDA2 uptake reflects changes in lesion content of OxLDL, in a separate study, extensive atherosclerosis was induced in 4 groups of LDLR-/- mice by feeding them a high fat/cholesterol diet for 6 months. A baseline group was euthanized at this time. The remaining groups were fed regression diets (chow or chow+1% vitamin E+0.05% vitamin C) or the high fat/cholesterol diet for 6 more months. When atherosclerosis was measured as percent surface area or aortic weight, there was strong progression in the high fat/cholesterol group, moderate progression in the chow group, and no progression in the chow+vitamin E+vitamin C group compared with the baseline group. The I-125-MDA2 method also yielded a significant increase in atherosclerosis in the high fat/cholesterol group but significant decreases in the chow and chow+vitamin E+vitamin C groups. Immunocytochemistry showed fewer oxidation-specific epitopes in lesions from the chow and chow+vitamin E+vitamin C groups. Thus, the uptake of I-125-MDA2 correlates well with traditional measures of atherosclerosis but also reflects reduced plaque OxLDL content after hypocholesterolemic intervention.
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