Antiatherosclerotic effects of a novel synthetic tissue-selective steroidal liver X receptor agonist in low-density lipoprotein receptor-deficient mice.

The Journal of Pharmacology and Experimental Therapeutics
Dacheng PengShutsung Liao

Abstract

Liver X receptor (LXR) agonists have the potential to treat atherosclerosis based on their ability to enhance reverse cholesterol transport. However, their side effects, such as induction of liver lipogenesis and triglyceridemia, may limit their pharmaceutical development. In contrast to the nonsteroidal LXR agonist N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317), 3alpha, 6alpha, 24-trihydroxy-24, 24-di(trifluoromethyl)-5beta-cholane (ATI-829), a novel potent synthetic steroidal LXR agonist, was a poor inducer of sterol regulatory element-binding protein 1c expression in hepatoma HepG2 cells, whereas both compounds increased ABCA1 expression in macrophage THP-1 cells. In male low-density lipoprotein receptor-deficient mice, ATI-829 selectively activated LXR target gene expression in mouse intestines and macrophages but not in the liver. A significant increase in liver triglyceride and plasma triglyceriderich small very low-density lipoprotein (VLDL) was observed in T0901317 but not ATI-829-treated mice. Compared with vehicle-treated mice, atherosclerosis development was significantly inhibited in the innominate artery after treatment with either compound. H...Continue Reading

References

Dec 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·L B NielsenK Kjeldsen
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·C SongS Liao
Oct 31, 1998·Current Opinion in Genetics & Development·D J PeetD J Mangelsdorf
Oct 29, 2000·The American Journal of Cardiology·P Cullen
Nov 23, 2000·Genes & Development·J R SchultzB Shan
Mar 10, 2001·Cell·C K Glass, J L Witztum
Jun 9, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·C A ReardonG S Getz
Sep 20, 2001·The Journal of Biological Chemistry·Y ZhangD J Mangelsdorf
Aug 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Rajendra K TangiralaIra G Schulman
Nov 2, 2002·Nature Medicine·Andrew C Li, Christopher K Glass
May 9, 2003·The Journal of Biological Chemistry·Shawn WilliamsTimothy M Willson
Jun 7, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Catherine A ReardonGodfrey S Getz
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Nov 8, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Paul A VanderLaanGodfrey S Getz
Mar 3, 2004·Drug News & Perspectives·Guoqing CaoPatrick I Eacho
May 18, 2004·The Journal of Clinical Investigation·Mitsuhiro WatanabeJohan Auwerx
Aug 5, 2004·Journal of Lipid Research·Elaine M QuinetPonnal Nambi
Sep 29, 2004·The Journal of Biological Chemistry·Christopher M AdamsJoseph L Goldstein
Nov 13, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Nancy LevinIra G Schulman
Aug 30, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Stefan R Bornstein, Henning Morawietz
Mar 3, 2006·The Journal of Clinical Investigation·Noam Zelcer, Peter Tontonoz
Mar 25, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Nan WangAlan R Tall
Feb 17, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Patricia G YanceySergio Fazio
Sep 26, 2007·Annals of the New York Academy of Sciences·Zoltán SzekaneczPál Soltész
Dec 22, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Minjia ZhuYi Zhu

❮ Previous
Next ❯

Citations

Mar 16, 2012·Current Atherosclerosis Reports·Daryn R MichaelDipak P Ramji
Oct 12, 2010·Cardiology in Review·Neil Parikh, William H Frishman
Jul 16, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Anna C Calkin, Peter Tontonoz
Feb 26, 2014·Cancer Cell International·Wenjun ZhangXiangbin Yuan
May 17, 2014·Nature Reviews. Drug Discovery·Cynthia Hong, Peter Tontonoz
Feb 13, 2010·Annual Review of Physiology·Pengxiang HuangFraydoon Rastinejad
Nov 20, 2012·Trends in Endocrinology and Metabolism : TEM·Barbara Bonamassa, Antonio Moschetta
Apr 7, 2010·Progress in Lipid Research·Maaike H OosterveerFolkert Kuipers
Feb 9, 2010·Atherosclerosis·Michael L FitzgeraldNorimasa Tamehiro
Jan 12, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yan-Wei HuQian Wang
Jul 15, 2011·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Michele VaccaAntonio Moschetta
Feb 9, 2012·British Journal of Clinical Pharmacology·Inge De MeyerGuido R Y De Meyer
Jul 15, 2015·Atherosclerosis·Stephen D Lee, Peter Tontonoz
Jul 6, 2013·Expert Opinion on Therapeutic Patents·Jon LorenValentina Molteni
Dec 3, 2014·Cancer Treatment Reviews·Mani Roshan-MoniriPaul S Rennie
Mar 29, 2014·Journal of Lipid Research·Tamer SallamCynthia Hong
Jul 30, 2014·Journal of Lipid Research·Chiara DegirolamoAntonio Moschetta
Jul 26, 2017·Journal of Medicinal Chemistry·Maura MarinozziVincenzo Russo
Mar 23, 2010·Expert Opinion on Therapeutic Patents·Xiaolin LiValentina Molteni
Jul 2, 2015·The Journal of Pharmacology and Experimental Therapeutics·Ali RamezaniMichael Bukrinsky
Jan 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rajesh KomatiGuangdi Wang
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Evan D MuseChristopher K Glass
Oct 25, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Irene PierantonelliGianluca Svegliati-Baroni
Dec 18, 2020·Bone·Divya Goel, Divya Vohora
May 17, 2014·Journal of Medicinal Chemistry·Colin M TiceSuresh B Singh
Feb 23, 2012·Biochimica Et Biophysica Acta·Makoto AyaoriKatsunori Ikewaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.