Characterization of lipoprotein in a kindred with familial hypercholesterolemia

W. Patsch, R. Ostlund, I. Kuisk, R. Levy, G. Schonfeld

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To study possible consequences of decreased numbers of cellular LDL receptors on plasma lipoproteins, we characterized the low density and high density lipoproteins in fasting plasmas of a kindred with receptor-defective hypercholesterolemia. The flotation rates (S(f)(o) 1.063) of the major LDL populations, determined by analytic ultracentrifugation, ranged from 4.7 to 7.4; densities (d 20) ranged from 1.0348 to 1.0402 g/ml and minimum molecular weights ranged from 2.5 to 3.5 x 10 6. On rate zonal ultracentrifugation, the major populations of LDL isolated from individual members of this kindred could be divided into fast and slow floating varieties. Fast floating LDL had a molecular weight >3.15 x 10 6, slow floating, <2.85 x 10 6. Both fast and slow floating LDL were found among affected members of the kindred. From molecular weights and chemical compositions, the numbers of molecules of lipid components per LDL particle were calculated. Numbers of phospholipid, free cholesterol, and cholesteryl ester molecules were each strongly correlated with the molecular weights of the LDL particles. Thus, the differences in mass of LDL resulted from alterations primarily of the phospholipid, free cholesterol, and cholesteryl ester contents per particle, whereas the amounts of protein and triglyceride per particle were relatively constant. An important and consistent finding of this study is that the LDL of members of the kindred affected with familial hypercholesterolemia (FH) differed from LDL of unaffected members by containing more molecules of cholesteryl ester and less triglyceride, even when LDL were matched for molecular weight. Thus, FH per se affected the core lipid composition of LDL. The mechanisms responsible for the change are unknown. Analysis of the distribution of LDL masses in this pedigree is compatible with genetic factors having some influence on LDL mass, but the great overlap of LDL mass between affected and nonaffected subjects implies that, whatever genetic or other factors limit LDL mass, these factors remain operative in FH. 'Hepatic' apoB (B-100, B-74, and B-26) comprised 96% of the protein moiety in all subjects, while 'intestinal' apoB (B-48) was not found in any of the LDL preparations. Therefore, LDL of both normal and affected members probably is derived from hepatic lipoproteins, HDL-cholesterol was low in children with Fh, but it was also low in an unaffected child and there was no correlation between the presence or absence of HDL 2 and FH status. There appeared to be a tendency toward lower LDL-cholesterol in those affected subjects whose plasma contained HDL 2. However, this suggestive inverse relationship between LDL and HDL 2 needs confirmation.

Original languageEnglish
Pages (from-to)1196-1205
Number of pages10
JournalJournal of lipid research
Issue number8
StatePublished - 1982


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