LIPOPROTEIN LIPASE-ENHANCED BINDING OF LIPOPROTEIN(A) [LP(A)] TO HEPARAN-SULFATE IS IMPROVED BY APOLIPOPROTEIN-E (APOE) SATURATION - SECRETION-CAPTURE PROCESS OF APOE IS A POSSIBLE ROUTE FOR THE CATABOLISM OF LP(A)

Recently, it has been recognized that cell-bound heparan sulfate (HS) proteoglycans (HSPG) are able to bind and subsequently initiate degrad ation of lipoproteins, Two mediators of lipoprotein catabolism, both w ith HS binding capacity, lipoprotein lipase (LPL) and apolipoprotein E (apoE), are involved in this process, This mechanism is known as the secretion-capture process of apoE, Lipoprotein(a) [Lp(a)] was shown to have a strong binding capacity to cell-associated HSPG. This binding capacity was increased by LPL addition, We investigated the effects of recombinant apoE (r-apoE) enrichment of Lp(a) on the binding to HS, L p(a), isolated by ultracentrifugation and gel filtration, was incubate d with r-apoE and reisolated by ultracentrifugation, resulting in r-ap oE-enriched Lp(a). ApoE-enriched Lp(a) and control Lp(a) were coated t o microtiter plates, The capacity to bind biotin;conjugated HS (b-HS) in the presence or absence of inactivated bovine LPL was studied. R-ap oE-enriched Lp(a) showed increased b-HS binding capacity versus contro l Lp(a). Addition of LPL resulted in an increased b-HS binding capacit y of both control and r-apoE-enriched Lp(a), To investigate whether bi nding of Lp(a) to endothelial cell HSPG occurred in vivo, 39 volunteer s were injected with heparin (50 U/kg) and plasma lipid and Lp(a) leve ls were determined before and 20 minutes after heparin injection. No s ignificant increase in plasma Lp(a) concentrations was found, The resu lts showed that Lp(a) can be enriched with apoE and that this resulted in increased LPL-enhanced binding to HSPG. From the in vitro studies, it can be concluded that the secretion-capture process of apoE is a p ossible catabolic route for Lp(a). However, whether this also occurs i n vivo remains to be confirmed. Copyright (C) 1997 by W.B. Saunders Co mpany.