Catabolism of apoprotein A-1 of HDL in normal and nephrotic rats

High density lipoprotein was isolated from the plasma of control and puromycin aminonucleoside nephrotic rats and labeled with ¹²⁵I. It was injected into control and nephrotic rats and the plasma analyzed after 3 min, 5 hr, and 20 hr. High density lipoprotein was isolated and the specific activity of apo A-I determined following apoprotein separation using SDS-polyacrylamide gel electrophoresis. The distribution of labeled apoproteins was determined in whole plasma by SDS-gel filtration column chromatography and the plasma concentration of apo A-I was calculated from its specific activity and the total plasma apo A-I radioactivity. A 3 min to 5 or 20 hr fractional catabolic rate was calculated. When multiplied by the plasma concentration of apo A-I, an estimate of the absolute catabolic rate was obtained. When injected into normal animals, the high density lipoprotein apo A-I had similar catabolic rates whether derived from control or nephrotic rat plasma, averaging 65 and 48 μg of apoprotein per ml of plasma per hr at 5 or 20 hr, respectively. Labeled HDL was injected into nephrotic rats of varying degrees of severity. The moderately nephrotic rats with plasma cholesterol levels averaging 177 mg/dl had apo A-I levels that were 3.6 times that of controls (1799 ± 195 μg/ml) and 2.4-fold increases in apo A-I catabolic rates (134 ± 28.9 μg/ml plasma/hr). The severely nephrotic rats with cholesterol concentrations averaging 396 mg/dl had apo A-I levels 7.1 times that of the controls (3533 ± 220 μg/ml) while the catabolic rate was 2.7 times the control rate (153 ± 19.5 μg/ml/hr), which was not a significant increase beyond that of the moderately nephrotic group. It was concluded that compositional differences of HDL resulting in an increased proportion of apo A-I, as in nephrotic rat plasma, do not affect apo A-I metabolism. The high levels of apo A-I in the plasma of nephrotic rats is due to increased hepatic synthesis that results in an expansion of the pool size and saturation of catabolic pathways. Small increases in apo A-I synthesis lead to large increases in the plasma concentration, an observation that may be important in the regulation of HDL levels that are known to be correlated with a decreased incidence of atherosclerosis.