Is the atherogenicity of Lp(a) caused by its reactivity with proteoglycans?
Apo B-containing lipoproteins from human plasma were studied for their ability to form complexes with glycosaminoglycans (GAG) and proteoglycans (PG) in the presence of Ca++ and Mg++ ions. We studied low density lipoproteins (LDL), Lp(a) as well as Lpa-, a particle generated from Lp(a) by removing the specific antigen (apo-a). The strongest reactivity with all apo B-containing lipoproteins was found with PG, followed by GAG isolated from human aorta, and by chondroitin-6-sulphate. Lp(a), on the other hand, formed complexes with the highest glycan:lipoprotein ratio using all three complexing agents. Treatment of Lp(a) with neuraminidase did not change the reactivity. The reactivity of Lpa-, on the other hand, was between that of Lp(a) and LDL. Lipoprotein glycan complexes were incubated with mouse peritoneal macrophages. This caused cholesterol ester accumulation and foam cell formation. The amount of cholesterol ester formed correlated highly significantly with the reactivity of a given lipoprotein with different glycans. Sera obtained from patients suffering from myocardial infarction (MI) were incubated with LDL and Lp(a) and the reisolated lipoproteins were also incubated with macrophages. Lipoproteins reisolated from MI plasma caused foam cell formation with MPM to a greater extent than reisolated material incubated with normal plasma. The highest cholesteryl ester accumulation was found when Lp(a) reisolated from MI plasma was incubated with MPM. These results may at least partly explain the higher atherogenicity of Lp(a) in comparison with LDL.
Kostner
G M
GM
Institute of Medical Biochemistry, University of Graz, Austria.
Bihari-Varga
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000502:physiology; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000502:physiology; D051379:Mice; D009203:Myocardial Infarction / Q000097:blood; D011509:Proteoglycans / Q000502:physiology*
D006025:Glycosaminoglycans; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans