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Your search keyword '"Kostner, Gert M."' showing total 183 results
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183 results on '"Kostner, Gert M."'

4. New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk

Author

Klose, Gerald, Beil, Frank Ulrich, Dieplinger, Hans, von Eckardstein, Arnold, Föger, Bernhard, Gouni-Berthold, Ioanna, Heigl, Franz, Koenig, Wolfgang, Kostner, Gert M., Landmesser, Ulf, Laufs, Ulrich, Leistikow, Frank, März, Winfried, Noll, Georg, Parhofer, Klaus G., Paulweber, Bernhard, Riesen, Walter F., Schaefer, Jürgen R., Steinhagen-Thiessen, Elisabeth, Steinmetz, Armin, Toplak, Hermann, Wanner, Christoph, and Windler, Eberhard

Published
2014
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6. Farnesoid X receptor represses hepatic human APOA gene expression

Author

Chennamsetty, Indumathi, Claudel, Thierry, Kostner, Karam M., Baghdasaryan, Anna, Kratky, Dagmar, Levak-Frank, Sanja, Frank, Sasa, Gonzalez, Frank J., Trauner, Michael, and Kostner, Gert M.

Subjects
Gene expression -- Physiological aspects, Bile acids -- Measurement -- Health aspects, Promoters (Genetics) -- Properties, Blood plasma -- Genetic aspects, Health care industry
Abstract

High plasma concentrations of lipoprotein(a) [Lp(a), which is encoded by the APOA gene] increase an individual's risk of developing diseases, such as coronary artery diseases, restenosis, and stroke. Unfortunately, increased Lp(a) levels are minimally influenced by dietary changes or drug treatment. Further, the development of Lp(a)-specific medications has been hampered by limited knowledge of Lp(a) metabolism. In this study, we identified patients suffering from biliary obstructions with very low plasma Lp(a) concentrations that rise substantially after surgical intervention. Consistent with this, common bile duct ligation in mice transgenic for human APOA (tg-APOA mice) lowered plasma concentrations and hepatic expression of APOA. To test whether farnesoid X receptor (FXR), which is activated by bile acids, was responsible for the low plasma Lp(a) levels in cholestatic patients and mice, we treated tg-APOA and tg-APOA/[Fxr.sup.-/-] mice with cholic acid. FXR activation markedly reduced plasma concentrations and hepatic expression of human APOA in tg-APOA mice but not in tg-APOA/[Fxr.sup.-/-] mice. Incubation of primary hepatocytes from tg-APOA mice with bile acids dose dependently downregulated APOA expression. Further analysis determined that the direct repeat 1 element between nucleotides -826 and -814 of the APOA promoter functioned as a negative FXR response element. This motif is also bound by hepatocyte nuclear factor 4α (HNF4α), which promotes APOA transcription, and FXR was shown to compete with HNF4α for binding to this motif. These findings may have important implications in the development of Lp(a)-lowering medications., Introduction Lipoprotein(a) [Lp(a)] is a plasma lipoprotein found in humans and Old World monkeys but is absent in conventional laboratory animals. Plasma Lp(a) concentrations are under strict genetic control and [...]

Published
2011
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7. Solution structure of human apolipoprotein(a) kringle IV type 6

Author

Maderegger, Bernhard, Bermel, Wolfgang, Hrzenjak, Andelko, Kostner, Gert M., and Sterk, Heinz

Subjects
Apolipoproteins -- Analysis, Proteins -- Structure, Structure-activity relationships (Biochemistry) -- Analysis, Lipoproteins -- Research, Amino acids -- Structure-activity relationships, Biological sciences, Chemistry
Abstract

The secondary structure of human apolipoprotein(a) KIVT6 consists of antiparallel beta-sheet , a parallel beta-sheet, and a helix containing residues Trp62-Tyr64 and Trp72-Tyr74, Cys1-Tyr2 and Thr78-Gln79, and Thr38-Tyr40, respectively.

Published
2002

8. A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32

Author

Varret, Mathilde, Rabes, Jean-Pierre, Saint-Jore, Bruno, Cenarro, Ana, Marinoni, Jean-Christophe, Civeira, Fernando, Devillers, Martine, Krempf, Michel, Coulon, Monique, Thiart, Rochelle, Kotze, Maritha J., Schmidt, Helena, Buzzi, Jean-Claude, Kostner, Gert M., Bertolini, Stephano, Pocovi, Miguel, Rosa, Alberto, Farnier, Michel, Martinez, Maria Montoya, Junien, Claudine, and Boileau, Catherine

Subjects
Genetic disorders -- Research, Chromosome mapping -- Usage, Hypercholesterolemia -- Genetic aspects, Biological sciences
Abstract

Autosomal dominant hypercholesterolemia (ADH), one of the most common hereditary disorders, maps to 1p34.1-p32 and is genetically more heterogeneous than usually thought. One large French pedigree and 12 other white families with ADH were identified, and linkage to LDLR and APOB were excluded. A new locus was implicated. ADH is characterized by an isolated elevation of LDL particles, brings premature mortality, and is usually thought to come from mutations in the LDLR and APOB genes.

Published
1999

13. High-level expression of various apolipoprotein(a) isoforms by 'transferrinfection': the role of kringle IV sequences in the extracellular association with low-density lipoprotein

Author

Frank, Sasa, Krasznai, Krisztina, Durovic, Srdan, Lobentanz, Eva-Maria, Dieplinger, Hans, Wagner, Ernst, Zatloukal, Kurt, Cotten, Matt, Utermann, Gerd, Kostner, Gert M., and Zechner, Rudolf

Subjects
Apolipoproteins -- Research, Transferrin -- Research, Low density lipoproteins -- Research, Biological sciences, Chemistry
Abstract

A 'transferrinfection' apolipoprotein a (apo(a)) system involving transferrin receptor- and adenovirus receptor-mediated DNA influx into cells allows the characterization of the function of kringle IV sequence during the extracellular attachment of low-density lipoprotein (LDL) and indicates that several kringle IV sequences are essential for the attachment other than kringle IV-36. Mixing of normal human plasma LDL and 18, 15 or 9 kringle IV repeats results in stable complexes, while site-directed mutagenesis of Arg residue results in the inhibition of extracellular attachment. The r-apo(a) carbohydrate moiety has no effect on the extracellular attachment of LDL, implicating the occurrence of protein-protein interactions between apoB and r-apo(a).

Published
1994

22. High D-glucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions

Author

Graier, Wolfgang F., Simecek, Sabine, Kukovetz, Walter R., and Kostner, Gert M.

Subjects
Endothelium-derived relaxing factors -- Physiological aspects, Health, Physiological aspects
Abstract

Pretreatment of porcine aortic endothelial cells with high D-glucose results in enhanced endothelium-derived relaxing factor (EDRF) formation (39%) due to increased endothelial [Ca.sup.2+] release (57%) and [Ca.sup.2+] entry (97% ) [...]

Published
1996

28. Lipoprotein (a)

Author

Kostner, Gert M. and Krempler, Franz

Published
1992

40. Activation of microsomal cytochrome P450 mono-oxygenase by Ca2+ store depletion and its contribution to Ca2+ entry in porcine aortic endothelial cells

Author

Hoebel, Bernhard G, Kostner, Gert M, and Graier, Wolfgang F

Subjects
Manganese, Swine, Dexamethasone, Membrane Potentials, Enzyme Activation, 8,11,14-Eicosatrienoic Acid, Cytochrome P-450 Enzyme System, Microsomes, Papers, Animals, Calcium, Cattle, Clofibrate, Endothelium, Vascular, Aorta
Abstract

1. We investigated how microsomal cytochrome P450 mono-oxygenase (Cyp450 MO) is regulated in cultured porcine aortic endothelial cells. The hypothesis that a Cyp450 MO-derived metabolite links Ca2+ store depletion and Ca2+ entry was studied further. 2. Microsomal Cyp450 MO was monitored fluorometrically by dealkylation of 1-ethoxypyrene-3,6,8-tris-(dimethyl-sulphonamide; EPSA) in saponin permeabilized cells or in subcellular compartments. Endothelial Ca2+ signalling was measured by a standard fura-2 technique, membrane potential was determined with the potential-sensitive fluorescence dye, bis-(1,3-dibutylbarbituric acid) pentamethine oxonol (DiBAC4(5)) and tyrosine kinase was quantified by measuring the phosphorylation of a immobilized substrate with a horseradish peroxidase labelled phosphotyrosine specific antibody. 3. Depletion of cellular Ca2+ pools with inositol 1,4,5-trisphosphate (IP3), thapsigargin or cyclopiazonic acid activated microsomal Cyp450 MO. Similar to direct Ca2+ store depletion, chelating of intramicrosomal Ca2+ with oxalate stimulated Cyp450 MO activity, while changing cytosolic free Ca2+ failed to influence Cyp450 MO activity. These data indicate that microsomal Cyp450 MO is activated by depletion of IP3-sensitive stores. 4. Besides the common cytochrome P450 inhibitors, econazole, proadifen and miconazole, thiopentone sodium and methohexitone inhibited Cyp450 MO in a concentration-dependent manner. The physiological substrate of Cyp450 MO, arachidonic acid, inhibited EPSA dealkylation. In contrast to most other cytochrome P450 inhibitors used in this study, thiopentone sodium did not directly interfere with Ca2+ entry pathways, membrane hyperpolarization due to K+ channel activation or tyrosine kinase activity. 5. Inhibition of Cyp450 MO by thiopentone sodium diminished Ca2+/Mn2+ entry to Ca2+ store depletion by 43%, while it did not interfere with intracellular Ca2+ release by IP3 or thapsigargin. 6. Cyp450 MO inhibition with thiopentone sodium diminished autacoid-induced membrane hyperpolarization. 7. Induction of Cyp450 MO with dexamethasone/clofibrate for 72 h yielded increases in thapsigargin-induced Cyp450 MO activity (by 35%), Ca2+/Mn2+ entry (by 105%) and membrane hyperpolarization (by 40%). 8. The Cyp450 MO-derived compounds, 11,12 and 5,6-epoxyeicosatrienoic acids (EETs) yielded membrane hyperpolarization, insensitive to thiopentone sodium. 9. These data demonstrate that endothelial Cyp450 MO is activated by Ca2+ store depletion and Cyp450 MO produced compounds that hyperpolarize endothelial cells. 10. The data presented and our previous findings indicate that Cyp450 MO plays a crucial role in the regulation of store-operated Ca2+ influx. We propose that Cyp450 MO-derived EETs constitute a signal for Ca2+ entry activation and increase the driving force for Ca2+ entry by membrane hyperpolarization in porcine aortic endothelial cells.

Published
1997

45. Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity

Author

STRAUSS, Juliane G., primary, ZIMMERMANN, Robert, additional, HRZENJAK, Andelko, additional, ZHOU, Yonggang, additional, KRATKY, Dagmar, additional, LEVAK-FRANK, Sanja, additional, KOSTNER, Gert M., additional, ZECHNER, Rudolf, additional, and FRANK, Sasa, additional

Published
2002
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50. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Standardization Project for the Measurement of Lipoprotein(a). Phase 2: Selection and Properties of a Proposed Secondary Reference Material for Lipoprotein(a).

Author

Tate, Jillian R., primary, Berg, Kåre, additional, Couderc, Rémy, additional, Dati, Francesco, additional, Kostner, Gert M., additional, Marcovina, Santica M., additional, Rifai, Nader, additional, Sakurabayashi, Ikunosuke, additional, and Steinmetz, Armin, additional

Published
1999
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