Inhibitors for the In Vitro Assembly of Lp(a)

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Abstract
Lp(a) is composed of an LDL-like core and the glycoprotein apo(a). Current evidence strongly suggests that the assembly of this atherogenic lipoprotein proceeds outside the liver cells in a two-step fashion. In the first step, a loose complex is formed involving kringle-4 motifs in apo(a) and one or more Lys side chains in apoB-100. In the second step, this complex is stabilized by a disulfide bridge. Indications are that Lp(a) assembly is critical in the determination of plasma apo(a) concentrations. Therefore, we searched for substances that interfere with the first step of Lp(a) assembly. ε-Aminohexoic acid (ε-AHA), known as an inhibitor from earlier assembly studies, had an IC50 of 4.8 mmol/L. The IC50 of Pro, HO-p-aminobenzene sulfonamide, Lys, N-ε-acetyl-Lys, taurine, Glu, serotonin, and benzamidine were all >20 mmol/L. γ-Aminobutyric acid, spermine, and spermidine exhibited IC50 on the same order of magnitude as ε-AHA. The substances with the highest inhibitory action were tranexamic acid ...