LESIONED LOW-DENSITY-LIPOPROTEIN IN ATHEROSCLEROTIC APOLIPOPROTEIN E-DEFICIENT TRANSGENIC MICE AND IN HUMANS IS OXIDIZED AND AGGREGATED

We analyzed lesioned LDL in both atherosclerotic humans and in the apo E deficient (E degrees) mice and compared its characteristics to plasma LDL. Lesioned LDL, in comparison to plasma LDL, was minimally oxidized and aggregated. Upon incubation of E degrees-aortic lesions with (125)[I]-labeled LDL, a time-dependent oxidation of the lipoprotein occurred as evident by a rapid and substantial elevation in LDL-associated TBARS from 0.2 to 10.3 and 14.5 nmoles of MDA equivalents/mg LDL protein after 2 and 24 hours of incubation, respectively. Only minimal LDL aggregates could be detected after 2 hours of incubation. Extensive LDL aggregation (15%), however, occurred after 24h of incubation. Similar results were obtained on using human lesioned aortas. We conclude that both oxidation and aggregation of lesioned LDL could be the result of aortic lesioned-induced modification of the lipoprotein, and both of these modified forms of LDL can further contribute to the acceleration of the atherosclerotic process. (C) 1995 Academic Press, Inc.