© 1995 American Heart Association, Inc.
Articles |
Inhibitors for the In Vitro Assembly of Lp(a)
From the Medical Biochemistry Department, University of Graz, and the Second Department of Medicine, University Hospital of Vienna (Austria) (K.K.).
Correspondence to Prof Dr G.M. Kostner, Medical Biochemistry Department, Karl-Franzens-Universität, Harrachgasse 21/III, 8010 Graz, Austria.
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. 
-Aminohexoic acid (-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--acetyl-Lys, taurine, Glu, serotonin,
and benzamidine were all >20 mmol/L. 
-Aminobutyric acid,
spermine, and spermidine exhibited IC50 on the same
order of magnitude as -AHA. The substances with the highest
inhibitory action were tranexamic acid and
-aminovaleric acid. Seven of eight patients treated in a pilot
study with tranexamic acid (Cyclocapron) responded with a decrease of
plasma apo(a) of 18.5±8.2%. We suggest that substances that interfere
with the Lp(a) assembly are worth pursuing further for their usefulness
as therapeutic agents in reducing high plasma Lp(a) concentrations.
Key Words: tranexamic acid • fibrinolysis • drug treatment • atherosclerosis • recombinant apo(a)
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