The plasma and tissue turnover and distribution of two radio-iodine-labelled pig plasma low density lipoproteins.

Two classes of pig plasma low density lipoprotein (LDL1 and LDL2) with different densities and molecular sizes were isolated by zonal ultracentrifugation and were further purified by flotation. The peptide component was iodinated with 125I, and the labelled lipoprotein was injected intravenously. 125I-LDL1 turnover studies were performed on 22 3-4 month old female Large White pigs, and 125I-LDL2 turnover studies on 4 similar pigs. A biological screening experiment confirmed that the shape of the plasma activity curve was not a function of protein denaturation. The pattern of radioactivity decline in plasma was not affected by the degree of LDL iodination. 125I-LDL1 turnover: The curve of plasma radioactivity plotted against time over the first 5 days after injection could be resolved into two exponentials. The plasma biological half-life (T 1/2) was calculated from the slower exponential predominant from the second day. The mean T 1/2 over 2-5 days was 22.9 hr (range 17.2-28.5 hr). Multicompartmental analysis of the plasma decay curve using an open mammillary model gave a mean fractional catabolic rate per day for LDL1 of 1.4 (range 0.9-1.9). The mean T 1/2 was 0.26-0.31 times and the fractional catabolic rate 3.0-3.9 times those values found in two studies on adult humans. The tissue distribution of 125I was analysed in a series of 20 animals killed from 1.0 to 33.8 days after 125I-LDL1 injection. Most tissue 125I (86-89%) was protein bound. An appropriate correction was made to the 125I counts for retained plasma in liver and spleen (using 131I-albumin); retained plasma in other tissues was negligible. Highest 125I tissue levels were found in the liver, supporting other evidence that the liver may be the major site of LDL1 catabolism. After 2.06 and 4.06 days the livers in two animals contained 1.6% and 0.7% respectively of the total injected 125I, equal to 33% and 54% of the total plasma 125I at those times. The skin contained about one-third to one-ninth the 125I in the liver at various times. Distribution in other organs was quantitatively minimal. Higher levels of radioactivity were found in the intima and inner media of the aorta than in the outer media. These results suggest that plasma LDL in the pig diffuses through the endothelial surface into the arterial wall. These findings are confirmed by autoradiography. 125I-LDL2 turnover: Parallel studies of plasma 125I-LDL2 turnover and tissue distribution were performed. The plasma biological decay curve was multi-exponential, suggesting that LDL2 metabolism is complex, and possibly more rapid than that of LDL1 (LDL2 is smaller and denser than LDL1). The tissue distribution of 125I-LDL2 in these pigs was very similar to that of 125I-LDL1. As LDL1 and LDL2 differ in the amount of lipid they contain, they may have different roles to play in lipid transport, and there may be interconversion of one into the other at different sites. This hypothesis remains conjectural.