Medizinische Universität Graz - Research portal
Selected Publication:
Frank, S; Hrzenjak, A; Kostner, K; Sattler, W; Kostner, GM.
Effect of tranexamic acid and delta-aminovaleric acid on lipoprotein(a) metabolism in transgenic mice.
BBA, MOL CELL BIOL LIPIDS. 1999; 1438(1): 99-110.
Doi: 10.1016/S1388-1981(99)00044-X
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Frank Sasa
- Kostner Gerhard
- Co-authors Med Uni Graz
- Hrzenjak Andelko
- Sattler Wolfgang
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- Abstract:
- The assembly of lipoprotein(a) (Lp(a)) is a two-step process which involves the interaction of kringle-4 (K-IV) domains in apolipoprotein(a) (apo(a)) with Lys groups in apoB-100. Lys analogues such as tranexamic acid (TXA) or delta-aminovaleric acid (delta-AVA) proved to prevent the Lp(a) assembly in vitro. In order to study the in vivo effect of Lys analogues, transgenic apo(a) or Lp(a) mice were treated with TXA or delta-AVA and plasma levels of free and low density lipoprotein bound apo(a) were measured. In parallel experiments, McA-RH 7777 cells, stably transfected with apo(a), were also treated with these substances and apo(a) secretion was followed. Treatment of transgenic mice with Lys analogues caused a doubling of plasma Lp(a) levels, while the ratio of free:apoB-100 bound apo(a) remained unchanged. In transgenic apo(a) mice a 1. 5-fold increase in plasma apo(a) levels was noticed. TXA significantly increased Lp(a) half-life from 6 h to 8 h. Incubation of McA-RH 7777 cells with Lys analogues resulted in an up to 1. 4-fold increase in apo(a) in the medium. The amount of intracellular low molecular weight apo(a) precursor remained unchanged. We hypothesize that Lys analogues increase plasma Lp(a) levels by increasing the dissociation of cell bound apo(a) in combination with reducing Lp(a) catabolism.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acids - pharmacology
- Amino Acids, Neutral - pharmacology
- Animals - pharmacology
- Apolipoproteins A - blood
- Cell Line - blood
- Half-Life - blood
- Lipoprotein(a) - blood
- Lysine - administration and dosage
- Mice - administration and dosage
- Mice, Transgenic - administration and dosage
- Tranexamic Acid - pharmacology
- Transfection - pharmacology
- Find related publications in this database (Keywords)
- Atherosclerosis
- Extracellular Matrix
- Lipid Metabolism
- Lipoprotein