Role of the Kidney in Regulating the Metabolism of HDL in Rabbits:  Evidence That Iodination Alters the Catabolism of Apolipoprotein A-I by the Kidney

To evaluate the factors that regulate HDL catabolism in vivo, we have measured the clearance of human apoA-I from rabbit plasma by following the isotopic decay of 125I-apoA-I and the clearance of unlabeled apoA-I using a radioimmunometric assay (RIA). We show that the clearance of unlabeled apoA-I is 3-fold slower than that of 125I-apoA-I. The mass clearance of iodinated apoA-I, as determined by RIA, is superimposable with the isotopic clearance of 125I-apoA-I. The data demonstrate that iodination of tyrosine residues alters the apoA-I molecule in a manner that promotes an accelerated catabolism. The clearance from rabbit plasma of unmodified apoA-I on HDL3 and a reconstituted HDL particle (LpA-I) were very similar and about 3−4-fold slower than that for 125I-apoA-I on the lipoproteins. Therefore, HDL turnover in the rabbit is much slower than that estimated from tracer kinetic studies. To determine the role of the kidney in HDL metabolism, the kinetics of unmodified apoA-I and LpA-I were reevaluated in animals after a unilateral nephrectomy. Removal of one kidney was associated with a 40−50% reduction in creatinine clearance rates and a 34% decrease in the clearance rate of unlabeled apoA-I and LpA-I particles. In contrast, the clearance of 125I-labeled molecules was much less affected by the removal of a kidney; FCR for 125I-LpA-I was reduced by