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Heterogeneous lipoprotein (a) size isoforms differ by their interaction with the low density lipoprotein receptor and the low density lipoprotein receptor‐related protein/α 2 ‐macroglobulin receptor
Author(s) -
März Winfried,
Beckmann Angela,
Scharnagl Hubert,
Siekmeier Rüdiger,
Mondorf Uli,
Held Irmtraud,
Schneider Wolfgang,
Preissner Klaus T.,
Curtiss Linda K.,
Groß Werner,
Hüttinger Manfred
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81087-g
Subject(s) - ldl receptor , lipoprotein(a) , lipoprotein , low density lipoprotein , chemistry , receptor , apolipoprotein b , lrp1b , microbiology and biotechnology , biochemistry , biology , cholesterol
Lipoprotein (a) (Lp(a)) is a complex of low density lipoprotein (LDL) with apolipoprotein (apo) (a). To examine the size distribution of L p (a), plasma was separated by fast flow gel filtration and L p (a): B complexes were determined in the eluate by enzyme immunoassays, in which detection was performed with monoclonal antibodies specific for apoB Lp(a): B particles displayed apparent molecular masses ( M r ) of 2 × 10 6 to at least 10 × 10 6 . Lp(a) size isoforms differed by the expression of apoB epitopes and their interaction with cultured human skin fibroblasts. LDL was more effective in inhibiting binding, uptake, and degradation of low M r , Lp(a) than of high M r Lp(a). In contrast, Glu‐plasmmogen, α 2 ‐macroglobulin and tissue‐type plasminogen activator were more effective in competing for the cellular degradation of high 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 lipoprotein receptor‐related protein/α 2 ‐macroglobulin receptor (LRP) and to two other endosomal membrane proteins. We propose that the LDL receptor preferentially internalizes low M r Lp(a), whereas LRP may have a role in the clearance of high M r Lp(a).