Accumulation of125I-tyramine cellobiose-labeled low density lipoprotein is greater in the atherosclerosis-susceptible region of white carneau pigeon aorta and further enhanced once atherosclerotic lesions develop

Abstract

Previous studies have suggested that greater arterial concentrations of undegraded low density lipoprotein (LDL) and/or greater arterial rates of LDL degradation may play role(s) in determining regional differences in arterial susceptibility to atherosclerosis in rabbits (Schwenke and Carew, Arteriosclerosis 1989;9:895-918). The White Carneau (WC) pigeon is also useful for investigating potential mechanism(s) that might account for regional variation in arterial susceptibility to atherosclerosis because atherosclerosis develops predictably in the aorta at the level of the celiac bifurcation (atherosclerosis-susceptible celiac site). In this study we sought to determine whether the 125I-tyramine cellobiose (125I-TC) content 1 day after injecting 125I-TC-LDL ("125I-TC-LDL accumulation") would be greater in the celiac site in arteries of WC pigeons and whether 125I-TC-LDL accumulation would be exaggerated by cholesterol feeding. Because 125I-TC remains trapped in cells after cellular degradation, arterial sites that either degrade LDL at higher rates or contain higher concentrations of undegraded LDL or both will demonstrate greater 125I-TC-LDL accumulation. Young WC pigeons were studied while consuming a cholesterol-free diet and after consuming a cholesterol-containing diet for 1,2,4, and 8 weeks. In pigeons fed a cholesterol-free diet, 125I-TC-LDL accumulation in the celiac site was equivalent to 0.24±0.02 μg LDL cholesterol/cm2 aortic surface/day compared with only 0.14±0.02 μg LDL cholesterol/cm2/day for the adjacent aorta, which is resistant to atherosclerosis (atherosclerosis-resistant site) (p<0.025). In atherosclerotic lesions excised from the celiac site, 125I-TC-LDL accumulation was equivalent to 21±10 μg LDL cholesterol/cm2 aortic surface/day compared with 0.66±0.17 μg LDL cholesterol/cm2/day for the adjacent atherosclerosis-resistant site (p<0.001). During cholesterol feeding, 125I-TC-LDL cholesterol accumulation in the celiac site as a whole increased 30-fold compared with a fivefold increase in plasma LDL cholesterol. In comparison, 125I-TC-LDL cholesterol accumulation in the adjacent atherosclerosis-resistant arterial site increased at the same rate as the plasma LDL cholesterol, while 125I-TC-LDL cholesterol accumulation in two other relatively atherosclerosis-resistant arterial sites that we studied increased relatively little during cholesterol feeding. The results of this study suggest that differences in arterial 125I-TC-LDL accumulation, both those present in normal animals and those induced by cholesterol feeding, may contribute to the characteristic regional variation in arterial susceptibility to atherosclerosis in WC pigeons. Additional studies will be needed to determine whether this difference reflects differences in arterial permeability to LDL, retention of undegraded LDL within the arterial extracellular matrix, or the cellular metabolism of LDL.