Metabolic evidence for sequestration of low-density lipoprotein in abdominal aorta of normal rabbits

Abstract

In rabbits, atherosclerosis develops preferentially at branch sites compared with the adjacent uniform aorta. This study investigated the hypothesis that low-density lipoprotein (LDL) is “sequestered” (present in a form that exchanges slowly with plasma LDL) in the aortas of normal rabbits and that more LDL is sequestered at branch sites. Thus 33 normal rabbits were injected with LDL labeled with 125I-labeled tyramine cellobiose (125I-TC) to trace both undegraded LDL and aortic LDL degradation products. For 25 rabbits, LDL was also labeled with 131I to trace undegraded LDL alone. The time-dependent aortic 125I-TC and 131I accumulation was determined from 0.6 to 120 h after injection. Compartmental modeling provided metabolic evidence for sequestration of LDL at the branch ( P < 0.01) and uniform ( P < 0.005) abdominal aorta. Concentrations of sequestered LDL were 109 ± 28% higher ( P < 0.0005) for branch sites. LDL mean residence time was 23.5 ± 3.1 h for branch sites, 7.6 ± 3.5 h longer ( P < 0.05) than for the uniform abdominal aorta. Enhanced retention of higher concentrations of sequestered LDL at branch sites could account for the increased susceptibility of these aortic sites to atherosclerosis.