LIPOPROTEIN LIPASE-ENHANCED BINDING OF HUMAN TRIGLYCERIDE-RICH LIPOPROTEINS TO HEPARAN SULFATE - MODULATION BY APOLIPOPROTEIN E AND APOLIPOPROTEIN C

摘要

The objective of this study was to investigate whether compositional variation in apolipoprotein (ape) content of triglyceride-rich lipoproteins (TRLP) modulates binding of heparan sulfate proteoglycans (HSPG). Human TRLP was enriched with apoE and apoCs and the ability to bind biotin-conjugated heparan sulfate (b-HS) was studied in the presence or absence of heat-inactivated lipoprotein lipase (LPL). TRLP, associated with LPL, showed an increased capacity to bind b-HS compared with TRLP alone. Low density lipoproteins (LDL) bound both b-HS and LPL with a higher affinity than TRLP. ApoE enrichment of TRLP resulted in an enhanced binding of b-HS. Increased binding of b-HS to TRLP by the combination of apoE enrichment and LPL addition was found to be complementary, not affecting their individual binding capacity. TRLP enrichment with apoC led to the formation of an apoC-rich, apoE-poor particle; this alteration by itself did not change the ability to bind b-HS. ApoC enrichment of TRLP resulted in a reduced capacity to bind LPL and therefore a subsequently reduced capacity to bind b-HS, compared with control TRLP associated with LPL. Competition studies revealed that b-HS binding to TRLP was fully displaceable by lactoferrin but barely by heparan sulfate, dermatan sulfate, or chondroitin-4-sulfate. Using TRLP coated to microtiter wells and associated with LPL, the b-HS displacement patterns were comparable to those obtained with coated LDL in the presence or absence of LPL. The cell-free system that was used enabled us to identify the functions of apoC and apoE in the binding of TRLP to LPL and HSPG. Both LPL and apoE increased the ability of TRLP to bind HSPG. The apoC content of TRLP regulated the docking of TRLP to LPL. ApoC enrichment reduced the affinity or capacity of TRLP to LPL binding, and this has relevance for the lipolytic cascade.-van Barlingen, H. H. J. J., H. de Jong, D. W. Erkelens, and T. W. A. de Bruin. Lipoprotein lipase-enhanced binding of human triglyceriderich lipoproteins to heparan sulfate: modulation by apolipoprotein E and apolipoprotein C. [References: 51]