INCREASED AUTOANTIBODY TITERS AGAINST EPITOPES OF OXIDIZED LDL IN LDLRECEPTOR-DEFICIENT MICE WITH INCREASED ATHEROSCLEROSIS

Increasing evidence indicates that immune processes modulate atherogen esis. Oxidized LDL (Ox-LDL) is immunogenic, and autoantibodies recogni zing epitopes of Ox-LDL have been described in plasma and in atheroscl erotic lesions of several species. To determine whether the titer of s uch autoantibodies correlates with the extent of atherosclerosis, we f ollowed the development of antibodies against malondialdehyde-lysine, an epitope of Ox-LDL, in two groups of LDL receptor- deficient mice fo r 6 months. One group was fed an atherogenic diet (21% fat and 0.15% c holesterol) that resulted in marked hypercholesterolemia and extensive aortic atherosclerosis; the other group was fed regular rodent chow ( 4% fat) that did not alter plasma cholesterol levels and induced minim al atherosclerosis. Autoantibody titers significantly increased over t ime in the group on the atherogenic diet, whereas they remained consta nt in the chow-fed group. When data from both groups were pooled, a si gnificant correlation was found between the autoantibody titers and th e extent of atherosclerosis (r=.61, P<.01). Autoantibody titers also c orrelated with plasma cholesterol levels (r=.48, P<.05). These results suggest that the rise in autoantibody titers to an epitope of Ox-LDL in this murine model is partially determined by the extent of atherosc lerosis but could also be influenced by the degree of hypercholesterol emia or other factors that may influence lipid peroxidation.