Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3 - Role of ApoE

Lipoprotein retention by vascular extracellular matrix proteoglycans is imp ortant in atherogenesis; Proteoglycans bind apolipoprotein (apo)B- and apoE -containing lipoproteins. However, the colocalization of apoA-I and apoE wi th biglycan in atherosclerotic lesions suggests that vascular proteoglycans also may trap high density lipoproteins (HDLs), Because the major HDL subc lasses may be atheroprotective to different degrees, we investigated the ro le 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-35]SO4-biglycan, whereas apoE-containing HDL2 and HDL3 (HDL+E) did. The e xtent 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. A poE 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 resul ts in diminished biglycan binding of HDL3+E relative to HDL2+E. Reducing po sitive charges on lysine and arginine residues on HDL+E eliminated biglycan binding, suggesting an ionic interaction. Thus, apoE is an important deter minant of HDL binding to extracellular vascular proteoglycans and may play a role in HDL retention in the artery wall.