Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3: role of apoE.
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 HDL(2) and HDL(3) binding to the extracellular vascular proteoglycan, biglycan. ApoE-free HDL(2) and HDL(3) did not bind to purified [(35)S]SO(4)-biglycan, whereas apoE-containing HDL(2) and HDL(3) (HDL+E) did. The extent of binding correlated positively with the apoE content for both HDL(2) and HDL(3), although HDL(2)+E had a 3.5-fold higher affinity than did HDL(3)+E. ApoE on HDL(3) was cleaved into 22- and 12-kDa fragments, whereas apoE on HDL(2) remained intact. These results suggest that the cleaved apoE on HDL(3) results in diminished biglycan binding of HDL(3)+E relative to HDL(2)+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.
Olin
K L
KL
Departments of Medicine, University of Washington, Seattle, USA.
Potter-Perigo
S
S
Barrett
P H
PH
Wight
T N
TN
Chait
A
A
D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism; D058578:Biglycan; D008076:Cholesterol, HDL / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism*
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C546884:BGN protein, human; D058578:Biglycan; D008076:Cholesterol, HDL; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans