Abstract 14911: Induction Of Regression Of Atherosclerosis By The LXR-agonist R211945-a Multimodality Non-invasive Assessment And Comparison With Atorvastatin
Background: Liver-x-receptor (LXR)-agonists induce reversal cholesterol transport and modulate inflammation.
Objective: R211945, an LXR-agonist, promotes reverse cholesterol transport while mitigating metabolic side effects. In this study, we aimed to non-invasively measure the anti-atherosclerotic properties of R211945 in comparison to atorvastatin and controls using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT and dynamic contrast-enhanced MRI (DCE-MRI).
Methods: Twenty-one atherosclerotic New Zealand White (NZW) rabbits were divided into control, R211945 (3mg/kg orally) and atorvastatin (3mg/kg orally) groups. All groups underwent 18F-FDG-PET/CT and DCE-MRI at baseline, 1 month and 3 months after treatment initiation. Concomitantly, we monitored serum metabolic parameters and ATP-binding cassette transporter A1 (ABCA1) expression and performed histological analysis.
Results: 18F-FDG-PET/CT detected a decrease in average maximal standardized uptake value (SUV) in the R211945 group (p=0.001) indicating inflammation regression, the atorvastatin group displayed no significant change (p=0.60) indicating no progression or regression, whereas the control group demonstrated an increase (p=0.04) indicating progression. DCE-MRI detected a trend towards difference (p=0.06) in area under the curve (AUC) in the atorvastatin group suggesting a decrease in neovascularization. Macrophage and apolipoprotein B immunoreactivity was decreased in the R211945 and atorvastatin groups (each: p<0.0001 and p=0.0004, respectively) and R211945 decreased oxidized phospholipid immunoreactivity (p=0.02). ABCA1 expression was induced by R211945 at 1 and 3 months (p=0.007 and p=0.01, respectively) without causing an increase in triglycerides (p=0.87 and p=0.81, respectively).
Conclusions: Noninvasive imaging with 18F-FDG-PET, DCE-MRI and histological analysis demonstrate significant anti-atherosclerotic effects of the LXR-agonist R211945 in comparison to atorvastatin. The results underline the prospective therapeutic role of LXR-agonist therapy in atherosclerosis.
- © 2011 by American Heart Association, Inc.