| Inhibitors for the in vitro assembly of Lp(a). | |
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MedLine Citation:
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PMID: 7583555 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S Frank; S Durovic; K Kostner; G M Kostner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 15 ISSN: 1079-5642 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 1995 Oct |
Date Detail:
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Created Date: 1995-11-27 Completed Date: 1995-11-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1774-80 Citation Subset: IM |
Affiliation:
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Medical Biochemistry Department, University of Graz, Austria. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antifibrinolytic Agents / pharmacology*, therapeutic use Base Sequence Cell Line Female Humans Lipoprotein(a) / antagonists & inhibitors*, chemistry, metabolism Male Middle Aged Molecular Sequence Data Recombinant Proteins / antagonists & inhibitors*, chemistry, metabolism Tranexamic Acid / pharmacology*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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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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