URINARY-EXCRETION OF APO(A) FRAGMENTS - ROLE IN APO(A) CATABOLISM

The biosynthesis and assembly of lipoprotein(a) [Lp(a)], a marker for atherosclerotic disease, appears to be well understood. However, infor mation is lacking concerning the mode and site of Lp(a) catabolism. Ap o(a) is reported to be ex creted into the urine. To study the effect o f this pathway on the overall catabolism of Lp(a), urinary apo(a) was characterized by immunoblotting. More than 10 distinct apo(a) bands wi th molecular masses between 30 and 160 kD were observed. Apo(a) fragme nts were not complexed to apoB. In more than 30 individuals the size o f apo(a) bands was comparable irrespective of their apo(a) phenotype, although marked differences in the relative intensities of the bands w ere observed. Eight batches of 24-hour urine collections collected fro m 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 correlatio n was found between urinary apo(a) concentrations normalized to creati nine levels and plasma Lp(a) values (rho=0.659; P<.0001). Of the total plasma apo(a), 0.073%, ie, 121 mu g apo(a), was excreted in the form of apo(a) fragments in 24-hour urine samples from 12 healthy volunteer s. We conclude that the catabolism of Lp(a) via excretion of apo(a) fr agments accounts for <1% of the daily Lp(a) catabolism.