Low-density lipoprotein binding affinity of arterial wall proteoglycans: characteristics of a chondroitin sulfate proteoglycan subfraction.
The characteristics of an arterial wall chondroitin sulfate proteoglycan (CS-PG) subfraction that binds avidly to low-density lipoproteins (LDL) was studied. A large CS-PG was extracted from bovine aorta intima-media under dissociative conditions, purified by density-gradient centrifugation and gel filtration chromatography, and further subfractionated by affinity chromatography on LDL-agarose. A proteoglycan subfraction, representing 25% of the CS-PG, showed an elution profile (with dissociation from LDL-agarose occurring between 0.5 and 1.0 M NaCl) corresponding to that of heparin, heretofore considered to be the most strongly binding glycosaminoglycan with LDL. The proteoglycan subfraction which migrated as a single band on composite agarose-polyacrylamide gel electrophoresis contained chondroitin 6-sulfate, chondroitin 4-sulfate and dermatan sulfate in a proportion of 70:22:8. The core protein of the proteoglycan had an apparent molecular weight of 245,000, and contained approx. 33 glycosaminoglycan chains with an average molecular weight of 32,000. The CS-PG subfraction, like heparin, formed insoluble complexes in the presence of 30 mM Ca2+. Complexing of LDL with proteoglycan resulted in two classes of interactions with 0.1 and 0.3 proteoglycan monomer bound per LDL particle characterized by an apparent Kd of 4 and 21 nM, respectively. This indicates that multiple LDL particles bind to single proteoglycan monomers even at saturation. In contrast, LDL-heparin interactions showed a major component characterized by an apparent Kd of 151 nM and a Bmax of 9 heparin molecules per LDL particle. The occurrence of a potent LDL-binding proteoglycan subfraction within the family of arterial CS-PG may be of importance in terms of lipid accumulation in atherogenesis.
Srinivasan
S R
SR
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112.
Vijayagopal
P
P
Eberle
K
K
Radhakrishnamurthy
B
B
Berenson
G S
GS
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002417:Cattle; D002499:Centrifugation, Density Gradient; D002808:Chondroitin Lyases / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000032:analysis; D002845:Chromatography; D003871:Dermatan Sulfate / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D006493:Heparin / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008970:Molecular Weight; D011509:Proteoglycans / Q000378:metabolism*
D000596:Amino Acids; D011508:Chondroitin Sulfate Proteoglycans; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates; D002808:Chondroitin Lyases