Journal of Lipid Research (Feb 2009)
Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemias⃞
- Adelheid Kratzer,
- Marlene Buchebner,
- Thomas Pfeifer,
- Tatjana M. Becker,
- Georg Uray,
- Makoto Miyazaki,
- Shinobu Miyazaki-Anzai,
- Birgit Ebner,
- Prakash G. Chandak,
- Rajendra S. Kadam,
- Emine Calayir,
- Nora Rathke,
- Helmut Ahammer,
- Branislav Radovic,
- Michael Trauner,
- Gerald Hoefler,
- Uday B. Kompella,
- Guenter Fauler,
- Moshe Levi,
- Sanja Levak-Frank,
- Gerhard M. Kostner,
- Dagmar Kratky
Affiliations
- Adelheid Kratzer
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Marlene Buchebner
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Thomas Pfeifer
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Tatjana M. Becker
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Georg Uray
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Makoto Miyazaki
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Shinobu Miyazaki-Anzai
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Birgit Ebner
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Prakash G. Chandak
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Rajendra S. Kadam
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Emine Calayir
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Nora Rathke
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Helmut Ahammer
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Branislav Radovic
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Michael Trauner
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Gerald Hoefler
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Uday B. Kompella
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Guenter Fauler
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Moshe Levi
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Sanja Levak-Frank
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Gerhard M. Kostner
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Dagmar Kratky
- Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/3, 8010 Graz, Austria; Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria; Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria; Department of Pharmaceutical Sciences, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Institute of Biophysics, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Department of Ophthalmology, University of Colorado at Denver Health Science Center, 4200 East 9th Avenue, Denver, CO 80262; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Journal volume & issue
-
Vol. 50,
no. 2
pp. 312 – 326
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-3β-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 7α-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.
