Document Detail

Inhibitors for the in vitro assembly of Lp(a).
MedLine Citation:
PMID:  7583555     Owner:  NLM     Status:  MEDLINE    
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. epsilon-Aminohexoic acid (epsilon-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-epsilon-acetyl-Lys, taurine, Glu, serotonin, and benzamidine were all > 20 mmol/L. gamma-Aminobutyric acid, spermine, and spermidine exhibited IC50 on the same order of magnitude as epsilon-AHA. The substances with the highest inhibitory action were tranexamic acid and delta-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.
S Frank; S Durovic; K Kostner; G M Kostner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  15     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-27     Completed Date:  1995-11-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1774-80     Citation Subset:  IM    
Medical Biochemistry Department, University of Graz, Austria.
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MeSH Terms
Antifibrinolytic Agents / pharmacology*,  therapeutic use
Base Sequence
Cell Line
Lipoprotein(a) / antagonists & inhibitors*,  chemistry,  metabolism
Middle Aged
Molecular Sequence Data
Recombinant Proteins / antagonists & inhibitors*,  chemistry,  metabolism
Tranexamic Acid / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Antifibrinolytic Agents; 0/Lipoprotein(a); 0/Recombinant Proteins; 1197-18-8/Tranexamic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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