Residence time of low-density lipoprotein in the normal and atherosclerotic rabbit aorta

Previous results from this laboratory found that the arterial low-density lipoprotein (LDL) residence time in lesion-prone aortic sites was longer in hyperlipidemic rabbits before lesion formation than in the corresponding sites in normolipidemic rabbits. The calculation of residence time in the previous study assumed that the arterial wall was homogeneous; the present study reexamines the issue using a method that does not require such an assumption. The concentration of radiolabeled arterial LDL was measured in New Zealand White rabbits killed at several different times (0.5 to 72 hours) after injection of labeled LDL. Using a stochastic analysis, arterial LDL residence time was calculated from the pooled labeled arterial LDL measurements from these rabbits. In these studies, the arterial LDL residence times in normolipidemic and hyperlipidemic rabbits before lesion formation were similar in both the lesion-prone and -resistant sites. However, immediately upon development of early fatty streak lesions, the arterial LDL residence time increased dramatically. After only 16 days of cholesterol feeding, the residence time was 10 times longer in the lesioned aortic arch compared with similar tissue from normolipidemic rabbits (4 to 45 hours). After 21 days of cholesterol feeding, the residence time of LDL in the lesioned aortic arch increased to > 25-fold that of normolipidemic tissue. Similar results were observed in the lesioned tissue of the abdominal branchings. This early retention of LDL suggests that significant changes are taking place within the arterial wall during this critical stage of early lesion development.