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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Kratzer, A; Buchebner, M; Pfeifer, T; Becker, TM; Uray, G; Miyazaki, M; Miyazaki-Anzai, S; Ebner, B; Chandak, PG; Kadam, RS; Calayir, E; Rathke, N; Ahammer, H; Radovic, B; Trauner, M; Hoefler, G; Kompella, UB; Fauler, G; Levi, M; Levak-Frank, S; Kostner, GM; Kratky, D.
Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemia.
J Lipid Res. 2009; 50(2): 312-326. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Ahammer Helmut
Becker Tatjana
Buchebner Marlene
Chandak Prakash Gopal Das
Fauler Günter
Gallé Birgit
Hoefler Gerald
Kostner Gerhard
Kratky Dagmar
Kratzer Adelheid
Levak Sanja
Pfeifer Thomas
Radovic Branislav
Rathke Nora
Trauner Michael
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Number of Figures: 10
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Abstract:
Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism. LXR agonists have been shown to limit the cellular cholesterol content by inducing reverse cholesterol transport, increasing bile acid production, and inhibiting intestinal cholesterol absorption. Most of them, however, also increase lipogenesis via sterol regulatory element-binding protein-1c (SREBP1c) and carbohydrate response element-binding protein activation resulting in hypertriglyceridemia and liver steatosis. We report on the antiatherogenic properties of the steroidal liver X receptor agonist N,N-dimethyl-3beta-hydroxy-cholenamide (DMHCA) in apolipoprotein E (apoE)-deficient mice. Long-term administration of DMHCA (11 weeks) significantly reduced lesion formation in male and female apoE-null mice. Notably, DMHCA neither increased hepatic triglyceride (TG) levels in male nor female apoE-deficient mice. ATP binding cassette transporter A1 and G1 and cholesterol 7alpha-hydroxylase mRNA abundances were increased, whereas SREBP1c mRNA expression was unchanged in liver, and even decreased in macrophages and intestine. Short-term treatment revealed even higher changes on mRNA regulation. Our data provide evidence that DMHCA is a strong candidate as therapeutic agent for the treatment or prevention of atherosclerosis, circumventing the negative side effects of other LXR agonists.
Find related publications in this database (using NLM MeSH Indexing)
ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism
Animals -
Apolipoproteins E - genetics Apolipoproteins E - metabolism
Atherosclerosis - drug therapy Atherosclerosis - pathology
Cholic Acids - therapeutic use
DNA-Binding Proteins - agonists DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism
Fatty Liver - chemically induced
Female -
Foam Cells - metabolism
Hypertriglyceridemia - chemically induced
Macrophages - metabolism
Male -
Mice -
Mice, Inbred C57BL -
Mice, Transgenic -
Orphan Nuclear Receptors -
RNA, Messenger - metabolism
Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism
Sterol Regulatory Element Binding Protein 1 - genetics Sterol Regulatory Element Binding Protein 1 - metabolism
Time Factors -

Find related publications in this database (Keywords)
atherogenesis
liver X receptor
cholesterol catabolism
ABC transporter
gene expression
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