Dietary alterations of plasma lipoproteins influence their interactions with proteoglycan enriched extracts from neointima of normal and injured aorta of rabbit.
The interactions between serum lipoproteins isolated from rabbits fed a cholesterol-supplemented diet for six weeks, and soluble extracts of arterial neointima enriched in proteoglycans extracted from normocholesterolaemic rabbit aortas, were studied in an in vitro system. Neointimal tissues of rabbit aorta, which developed during three months following a selective endothelial injury, were excised and the areas covered or uncovered by regenerated endothelium were separated. To isolate the proteoglycan enriched fraction, both normal and injured tissue was homogenized in a sucrose solution containing protease inhibitors, centrifuged, and further fractionated by gel exclusion chromatography. The composition of the soluble extracts and each of their corresponding proteoglycan enriched fractions were analyzed in terms of protein and glycosaminoglycan content. Lipoproteins of donor animals fed an atherogenic diet were prepared by sequential ultracentrifugal flotation after density adjustment with KBr. Aliquots of electrophoretically pure lipoprotein fractions were incubated with proteoglycan enriched fraction from uninjured, denuded, or endothelium-covered neointima in the presence of Ca++ and Mg++ at 4 degrees C. The complexes formed during incubation were separated by centrifugation. The cholesterol content of the complexes was considered as an index of binding capacity. Results were expressed as micrograms of cholesterol bound per mg of glycosaminoglycan. The data reveal the higher affinity of hypercholesterolaemic lipoprotein fractions for aortic proteoglycans, as compared to normocholesterolaemic lipoproteins. In addition, when evaluating the relevance of the proteoglycan enriched fraction source, the affinity of fractions extracted from aortic neointima was found to be much higher for hypercholesterolaemic lipoproteins. These results suggest the role that proteoglycan-lipoprotein interactions could play in the event of the combined actions of endothelial injury and hypercholesterolaemia in the pathogenesis of atherosclerosis.
Alavi
M Z
MZ
Department of Pathology, McGill University, Montreal, Quebec.
Galis
Z
Z
Li
Z H
ZH
Moore
S
S
D000818:Animals; D001011:Aorta / Q000737:chemistry*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D002809:Chondroitin Sulfates / Q000302:isolation & purification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology / Q000601:surgery; D005260:Female; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits
D002791:Cholesterol, Dietary; D006025:Glycosaminoglycans; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011509:Proteoglycans; D002809:Chondroitin Sulfates