Interaction of lipoprotein Lp(a) and low density lipoprotein with glycosaminoglycans from human aorta.
The lipoprotein complexing activity of glycosaminoglycans (GAG) prepared from human aortas with lipoprotein Lp(a) in comparison to low density lipoproteins (LDL) was determined tubidimetrically in the presence of Ca++. In control experiments, purified chondroitin-6 sulfate and proteoglycans (PG) were used. Lp(a) exhibited approximately a threefold higher reactivity. Analyzing the chemical composition of the complexes, we found that Lp(a) had greater than fourfold higher binding capacity for GAG. The binding capacity of Lp(a) to PG was 3.4-fold higher as compared to LDL. The binding capacity of both lipoproteins for chondroitin-6 sulfate was only 50% in comparison to GAG, but again Lp(a) was four times more reactive. Neuraminidase treatment of LDL or Lp(a) did not interfere with GAG or chondroitin-6 sulfate binding. If, on the other hand, Lp(a) was treated with dithiothreitol and the Lp(a)-specific protein (apoprotein [apo] a) was removed, the GAG binding was reduced by about 45%. Apo a by itself gave no insoluble complexes with GAG. LDL and Lp(a)-s GAG and -LP(a)-PG complexes were incubated with mouse peritoneal macrophages (MPM), and the stimulation of cholesteryl ester formation was studied. At identical lipoprotein cholesterol concentrations, Lp(a)-GAG complexes exhibited a 1.3-fold higher stimulation of cholesterol esterification as compared to LDL-GAG. This difference was even more striking if lipoproteins were compared at a molar basis. PG-lipoprotein complexes were much more active with respect to interactions with MPM. The highest amount of cholesterol ester formation upon incubation with MPM was found with PG-Lp(a) complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Bihari-Varga
M
M
Second Department of Pathology, Semmelweis Medical University, Hungary.
Gruber
E
E
Rotheneder
M
M
Zechner
R
R
Kostner
G M
GM
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D004229:Dithiothreitol; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D046911:Macromolecular Substances; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009391:Nephelometry and Turbidimetry; D009439:Neuraminidase; D011509:Proteoglycans / Q000378:metabolism
D006025:Glycosaminoglycans; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D011509:Proteoglycans; D009439:Neuraminidase; D004229:Dithiothreitol