In vivo uptake of radiolabeled MDA2, an oxidation-specific monoclonal antibody, provides an accurate measure of atherosclerotic lesions rich in oxidized LDL and is …
S Tsimikas, BP Shortal, JL Witztum… - … , and vascular biology, 2000 - Am Heart Assoc
S Tsimikas, BP Shortal, JL Witztum, W Palinski
Arteriosclerosis, thrombosis, and vascular biology, 2000•Am Heart AssocTo determine whether labeled antibodies against oxidized LDL (OxLDL) offer advantages
for quantifying atherosclerosis, we compared in vivo aortic uptake of 125I-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 125I-MDA2 were significantly …
for quantifying atherosclerosis, we compared in vivo aortic uptake of 125I-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 125I-MDA2 were significantly …
Abstract
—To determine whether labeled antibodies against oxidized LDL (OxLDL) offer advantages for quantifying atherosclerosis, we compared in vivo aortic uptake of 125I-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 125I-MDA2 were significantly greater in plaque than in normal aortas. Uptake of 125I-MDA2 significantly correlated with aortic weight and percent atherosclerotic surface area in rabbits and mice. To assess whether 125I-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 125I-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 125I-MDA2 correlates well with traditional measures of atherosclerosis but also reflects reduced plaque OxLDL content after hypocholesterolemic intervention.
Am Heart Assoc