Urinary Excretion of Apo(a) Fragments

The biosynthesis and assembly of lipoprotein(a) Lp(a), a marker for atherosclerotic disease, appears to be well understood. However, information is lacking concerning the mode and site of Lp(a) catabolism. Apo(a) is reported to be excreted into the urine. To study the effect of this pathway on the overall catabolism of Lp(a), urinary apo(a) was characterized by immunoblotting. More than 10 distinct apo(a) bands with molecular masses between 30 and 160 kD were observed. Apo(a) fragments were not complexed to apoB. In more than 30 individuals the size of apo(a) bands was comparable irrespective of their apo(a) phenotype, although marked differences in the relative intensities of the bands were observed. Eight batches of 24-hour urine collections collected from one proband at 2-week intervals exhibited a significant correlation between creatinine and apo(a) concentrations as measured by DELFIA (r = .93; P < .01). In 193 healthy volunteers a highly significant correlation was found between urinary apo(a) concentrations normalized to creatinine levels and plasma Lp(a) values (p = 0.659; P < .0001). Of the total plasma apo(a), 0.073%, i.e., 121 micrograms apo(a), was excreted in the form of apo(a) fragments in 24-hour urine samples from 12 healthy volunteers. We conclude that the catabolism of Lp(a) via excretion of apo(a) fragments accounts for < 1% of the daily Lp(a) catabolism.