title: Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: an magnetic resonance imaging study in a model of advanced atherosclerosis.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of liver X receptors (LXRs)-β preferential activation by LXR-623 (WAY-252623), a novel LXRs agonist, on plaque progression/regression in a rabbit model of advanced atherosclerosis.
  
  
  RESULTS
  Advanced atherosclerosis was induced in New Zealand White Rabbits (n= 41). At the end of atherosclerosis induction, animals underwent a baseline magnetic resonance imaging (MRI) and were randomized to receive LXR-623 (1.5, 5, or 15 mg/kg/day), simvastatin (5 mg/kg/day), or placebo. The combination of LXR-1.5/simvastatin was also tested. After a final MRI, animals were euthanized and their aortas processed for further analysis. Simvastatin significantly reduced lesion progression (-25%; P< 0.01) in comparison with the placebo group. A similar effect was observed in the LXR-1.5 and -5 groups. A significant regression (16.5%; P< 0.01) of existing atherosclerosis was observed in the LXR-1.5/simvastatin group. Histological and molecular analysis showed plaque stabilization in the animals treated with the LXR-1.5 and -5, and LXR-1.5/simvastatin. The effects of LXR-623 were observed in the presence of a non-significant effect on total-cholesterol, low-density lipoproteins-cholesterol, and triglyceride levels.
  
  
  CONCLUSIONS
  The results of the present study show that LXR-623 significantly reduces the progression of atherosclerosis and induces plaque regression in combination with simvastatin. These observations could drive future development of novel anti-atherosclerotic therapeutic approaches.
authors: AtheroThrombosis Research Unit, Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: Chiara
authors: C
authors: Giannarelli
authors: Giovanni
authors: G
authors: Cimmino
authors: Thomas M
authors: TM
authors: Connolly
authors: Borja
authors: B
authors: Ibanez
authors: Josè M Garcia
authors: JM
authors: Ruiz
authors: Matilde
authors: M
authors: Alique
authors: M Urooj
authors: MU
authors: Zafar
authors: Valentin
authors: V
authors: Fuster
authors: Giora
authors: G
authors: Feuerstein
authors: Juan J
authors: JJ
authors: Badimon