HETEROGENEOUS LIPOPROTEIN (A) SIZE ISOFORMS DIFFER BY THEIR INTERACTION WITH THE LOW-DENSITY-LIPOPROTEIN RECEPTOR AND THE LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN ALPHA(2)-MACROGLOBULIN RECEPTOR

Lipoprotein (a) (Lp(a)) is a complex of low density lipoprotein (LDL) with apolipoprotein (apo) (a). To examine the size distribution of Lp( a), plasma was separated by fast flow gel filtration and Lp(a):B compl exes were determined in the eluate by enzyme immunoassays, in which de tection was performed with monoclonal antibodies specific for apoB. Lp (a):B particles displayed apparent molecular masses (M(r)) of 2 x 10(6 ) to at least 10 x 10(6). Lp(a) size isoforms differed by the expressi on of apoB epitopes and their interaction with cultured human skin fib roblasts. LDL was more effective in inhibiting binding, uptake, and de gradation of low M(r) Lp(a) than of high M(r) Lp(a). In contrast, Glu- plasminogen, alpha2-macroglobulin and tissue-type plasminogen activato r were more effective in competing for the cellular degradation of hig h M(r) Lp(a) than of low M(r) Lp(a). Ligand blotting revealed that Lp( a) bound to the low density lipoprotein receptor, the low density lipo protein receptor-related protein/alpha2-macroglobulin receptor (LRP) a nd to two other endosomal membrane proteins. We propose that the LDL r eceptor preferentially internalizes low M(r) Lp(a), whereas LRP may ha ve a role in the clearance of high M(r) Lp(a).