The well documented association between high plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular disease might be mediated by the lysine binding of apolipoprotein(a) (apo(a)), the plasminogen-like, multikringle glycoprotein in Lp(a). We employed a mutational analysis to localize the lysine-binding domains within human apo(a). Recombinant apo(a) (r-apo(a)) with 17 plasminogen kringle IV-like domains, one plasminogen kringle V-like domain, and a protease domain or mutants thereof were expressed in the human hepatocarcinoma cell line HepG2. The lysine binding of plasma Lp(a) and r-apo(a) in the culture supernatants of transfected HepG2 cells was analyzed by lysine-Sepharose affinity chromatography. Wild type recombinant Lp(a) (r-Lp(a)) revealed lysine binding in the range observed for human plasma Lp(a). A single accessible lysine binding site in Lp(a) is indicated by a complete loss of lysine binding observed for r-Lp(a) species that contain either a truncated r-apo(a) lacking kringle IV-37, kringle V, and the protease or a point-mutated r-apo(a) with a Trp-4174-->Arg substitution in the putative lysine-binding pocket of kringle IV-37. Evidence is also presented for additional lysine-binding sites within kringles 32-36 of apo(a) that are masked in Lp(a) as indicated by an increased lysine binding for the point mutant (Cys-4057-->Ser), which is unable to assemble into particles. An important role of these lysine-binding site(s) for Lp(a) assembly is suggested by a decreased assembly efficiency for deletion mutants lacking either kringle 32 or kringles 32-35.

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We found no significant difference in the distribution of Apo E phenotypes between patients with CJD and controls. The concentration of Apo E in cerebrospinal fluid cannot be taken as a biochemical marker for the disease. The Apo E phenotype had no influence on the duration of CJD. Our data do not support an association of Apo E4 with either the duration or time at onset of CJD.

To evaluate serum apo AI, apo B, Lp(a) and the ratio of unesterified cholesterol to total cholesterol as markers of hepatic synthetic capacity after orthotopic liver transplantation, serial measurements of these variables were performed on post-transplant days 1, 3, 5, 7, 10 and 14 in 70 patients. Liver function was assessed by a quantitative dynamic test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX). Patients were divided into two groups on the basis of clinical and laboratory findings, those with evidence (n = 46) and those without evidence (n = 24) of hepatic dysfunction. Apo AI levels fell in both groups to day 5, but then began to increase in the group with good hepatic function, a highly significant (P < 0.001) positive correlation being found with the results of the MEGX test on post-transplant days 7, 10 and 14. The ratio of unesterified cholesterol to total cholesterol rose in both groups from days 1 to 7 and then began to fall in the group without hepatic dysfunction; a highly significant (P < 0.001) negative correlation was observed with the results of the MEGX test on days 10 and 14, Apo B levels rose in both groups from days 1 to 10, with no significant differences between the two groups; no correlation was observed with the results of the MEGX test on any study day.(ABSTRACT TRUNCATED AT 250 WORDS)

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