The NH2-terminal region of apolipoprotein B is sufficient for lipoprotein association with glycosaminoglycans

An initial event in atherosclerosis is the retention of lipoproteins within the intima of the vessel wall. The co-localization of apolipoprotein (apo) B and proteoglycans within lesions has suggested that retention is due to Lipoprotein interaction with these highly electronegative glycoconjugates. Both apoB100- and apoB48-eontaining lipoproteins, i.e. low density lipoprot eins (LDLs) and chylomicron remnants, are atherogenic, This suggests that r etention is due to determinants in the initial 48% of apoB, To test this, t he interaction of an apoB fragment (apoB17), and apoB48- and apoB100- conta ining lipoproteins with heparin, subendothelial matrix, and artery wall pur ified proteoglycans was studied. ApoB100-containing LDL from humans and hum an apoB transgenic mice and apoB48-containing LDLs from apoE knockout mice were used. Despite the lack of the carboxyl-terminal 52% of apoB, the apoB4 8-LDL bound to heparin-affinity gel as well as did apoB100-LDL, An NH2-term inal fragment containing 17% of full-length apoB was made using a recombina nt adenovirus; apoB17 bound to heparin as well as did LDL, Monoclonal antib odies against the NH2-terminal region of apoB decreased apoB100 LDL binding to heparin, whereas antibodies against the LDL receptor-binding region did not alter LDL-heparin interaction. The role of the NH2-terminal region of apoB in LDL interaction with matrix molecules was also assessed. Media cont aining apoB17 decreased LDL binding to subendothelial matrix by 42%, Moreov er, removal of the apoB17 by immunoprecipitation abrogated the inhibitory e ffect of these media, Antibodies to the NH2-terminal region decreased LDL b inding to matrix and dermatan sulfate proteoglycans. Purified apoB17 effect ively competed for binding of LDL to artery derived decorin and to subendot helial matrix. Thus, despite the presence of multiple basic amino acids nea r the LDL receptor-binding domain of LDL, the NH2-terminal region of apoB i s sufficient for the interaction of lipoproteins with glycoconjugates produ ced by endothelial and smooth muscle cells. The presence of a proteoglycan- binding site in the NH2-terminal region of apoB may explain why apoB48- and apoB100-containing lipoproteins are equally atherogenic.