Modifications of low-density lipoprotein induced by arterial proteoglycans and chondroitin-6-sulfate.
Association of low-density lipoproteins (LDL) with arterial chondroitin sulfate proteoglycans (CSPG) appears to contribute to their deposition in the extracellular intimal compartment and to its internalization by macrophages. CSPG and LDL interact by ionic bridges with formation of soluble and insoluble complexes. We studied the alterations on LDL structure induced by its association with arterial CSPG and other glycosaminoglycans (GAG). In soluble complexes, at low and at physiological ionic strength, arterial CSPG and sulfated GAG modify the kinetics of apoB-100 proteolysis by trypsin. However, less marked alterations in the peptide patterns were observed with proteinase V8 and almost none with thermolysin. This is indirect evidence that the presence of CSPG and GAG modified the exposure of polar regions of apoB-100 in LDL. Competitive binding experiments with agarose-bound heparin and soluble GAG also suggest that after formation of insoluble complexes with arterial CSPG and resolubilization the exposure of Lys, Arg-rich segments of apoB-100 is increased. Results from differential scanning calorimetry and differential thermal spectrophotometry showed that the CSPG and GAG-induced modifications reduced the thermal stability of the surface and core in LDL. If present in vivo, the structural alterations of polar segments of the LDL protein moiety may influence the outcome of its interaction with the arterial mesenchyma.
Camejo
G
G
Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden.
Hurt
E
E
Wiklund
O
O
Rosengren
B
B
López
F
F
Bondjers
G
G
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D001667:Binding, Competitive; D002152:Calorimetry, Differential Scanning; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006025:Glycosaminoglycans / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D014357:Trypsin
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D014357:Trypsin