Metabolism of native and acetylated low density lipoproteins in squirrel monkeys with emphasis on aortas with varying severities of atherosclerosis.

We studied the clearance of 131I-labeled native low density lipoproteins (LDL) and 125I-acetyl LDL from the blood of hypercholesterolemic and atherosclerotic squirrel monkeys which had been fed a semipurified diet supplemented with cholesterol for 3 years and from control monkeys which had been fed the same diet without cholesterol. In agreement with previous observations in other species, acetyl LDL left the circulation much more rapidly than native LDL. The cholesterol supplemented monkeys removed native 131I-LDL to the liver, the major site of clearance of both LDL forms, more slowly than controls. The overall clearance of 125I-acetyl LDL was similar for the two groups. The aortic intima plus inner media (AIM) cleared both LDL forms much more slowly than other organs, and the ratio of acetyl LDL to native LDL cleared was quite high. The outer media (OM) showed less selectivity for acetyl LDL than the AIM. While LDL clearance by the OM was not affected by diet, the LDL clearance per g of AIM tissue was increased by 2-fold for both native and acetyl LDL in the cholesterol supplemented monkeys. These monkeys also had a 3-fold increase in AIM weight (due to intimal and subintimal thickening), which resulted in a 6-fold increase in the total LDL cleared by the AIM. The clearance of both LDL forms by the AIM correlated with three indices of atherosclerosis: intimal thickness, AIM weight, and AIM cholesterol concentration. The correlations were higher in the case of acetyl LDL clearance which may be due to the high affinity of the acetylated form for macrophages.