Biglycan, a Vascular Proteoglycan, Binds Differently to HDL2 and HDL3: Role of ApoE

Abstract—Lipoprotein retention by vascular extracellular matrix proteoglycans is important in atherogenesis. Proteoglycans bind apolipoprotein (apo)B- and apoE-containing lipoproteins. However, the colocalization of apoA-I and apoE with biglycan in atherosclerotic lesions suggests that vascular proteoglycans also may trap high density lipoproteins (HDLs). Because the major HDL subclasses may be atheroprotective to different degrees, we investigated the role of apoE in mediating HDL2 and HDL3 binding to the extracellular vascular proteoglycan, biglycan. ApoE-free HDL2 and HDL3 did not bind to purified [S]SO4-biglycan, whereas apoE-containing HDL2 and HDL3 (HDL+E) did. The extent of binding correlated positively with the apoE content for both HDL2 and HDL3, although HDL2+E had a 3.5-fold higher affinity than did HDL3+E. ApoE on HDL3 was cleaved into 22- and 12-kDa fragments, whereas apoE on HDL2 remained intact. These results suggest that the cleaved apoE on HDL3 results in diminished biglycan binding of HDL3+E relative to HDL2+E. Reducing positive charges on lysine and arginine residues on HDL+E eliminated biglycan binding, suggesting an ionic interaction. Thus, apoE is an important determinant of HDL binding to extracellular vascular proteoglycans and may play a role in HDL retention in the artery wall.