Specificity of the low density lipoprotein-glycosaminoglycan interaction.
There is ample documentation of the binding of chondroitin sulfate/dermatan sulfate proteoglycans to low density lipoprotein (LDL) both in vivo and in vitro. The interaction of these two species may be an early and important step in atherogenesis. Therefore, there is interest in defining the features of both molecules that are critical for their interaction. We employed a recently described competitive microassay that measures initial binding of proteoglycan to immobilized LDL. We confirmed the work of others that it is the apolipoprotein B component and, at least in part, a heparin-binding domain of LDL that are responsible for binding chondroitin sulfate/dermatan sulfate proteoglycans. The principal thrust of our study was concerned with the effects of a glycosaminoglycan's degree of sulfation on the binding to LDL. Initial experiments comparing dermatan sulfate and chondroitin sulfate proteoglycans indicated that the former was more efficient at binding LDL than the latter and that oversulfation, rather than chain length or iduronate content, was the preeminent feature involved. Additional binding studies with dermatan sulfate, chemically sulfated chondroitin-4-sulfate, and naturally occurring oversulfated chondroitin sulfates indicated that the degree of sulfation, not the position of sulfation, determined affinity for LDL. These results suggest that studies should be undertaken to determine whether oversulfated segments of glycosaminoglycans are especially involved in associations with LDL, leading to lipid accumulation, in the artery wall.
Sambandam
T
T
Department of Biochemistry, University of Alabama, Birmingham 35294.
Baker
J R
JR
Christner
J E
JE
Ekborg
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001055:Apolipoproteins B / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002813:Chondrosarcoma / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D013431:Sulfates / Q000378:metabolism
D000906:Antibodies; D001055:Apolipoproteins B; D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D013431:Sulfates; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate; D006493:Heparin