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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Chennamsetty, I; Kostner, KM; Claudel, T; Vinod, M; Frank, S; Weiss, TS; Trauner, M; Kostner, GM.
Nicotinic acid inhibits hepatic APOA gene expression: studies in humans and in transgenic mice.
J Lipid Res. 2012; 53(11):2405-2412
Doi: 10.1194/jlr.M029769
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- Führende Autor*innen der Med Uni Graz
- Chennamsetty Indumathi
- Kostner Gerhard
- Co-Autor*innen der Med Uni Graz
- Claudel Thierry
- Frank Sasa
- Trauner Michael
- Vinod Manjula
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- Abstract:
- Elevated plasma lipoprotein(a) (LPA) levels are recognized as an independent risk factor for cardiovascular diseases. Our knowledge on LPA metabolism is incomplete, which makes it difficult to develop LPA-lowering medications. Nicotinic acid (NA) is the main drug recommended for the treatment of patients with increased plasma LPA concentrations. The mechanism of NA in lowering LPA is virtually unknown. To study this mechanism, we treated transgenic (tg) APOA mice with NA and measured plasma APOA and hepatic mRNA levels. In addition, mouse and human primary hepatocytes were incubated with NA, and the expression of APOA was followed. Feeding 1% NA reduced plasma APOA and hepatic expression of APOA in tg-APOA mice. Experiments with cultured human and mouse primary hepatocytes in addition to reporter assays performed in HepG2 cells revealed that NA suppresses APOA transcription. The region between -1446 and -857 of the human APOA promoter harboring several cAMP response element binding sites conferred the negative effect of NA. In accordance, cAMP stimulated APOA transcription, and NA reduced hepatic cAMP levels. It is suggested that cAMP signaling might be involved in reducing APOA transcription, which leads to the lowering of plasma LPA.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apolipoproteins A - genetics Apolipoproteins A - metabolism
- Atherosclerosis - genetics Atherosclerosis - metabolism
- Cells, Cultured -
- Cyclic AMP - pharmacology
- Gene Expression - drug effects
- Hep G2 Cells -
- Hepatocytes - drug effects Hepatocytes - metabolism
- Humans -
- Liver - drug effects Liver - metabolism
- Mice -
- Mice, Transgenic -
- Niacin - pharmacology
- RNA, Messenger -
- Find related publications in this database (Keywords)
- primary human hepatocytes
- reporter assay
- apolipoprotein(a)
- mRNA expression
- atherosclerosis