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- W1986381254 abstract "P482 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2 NOVEL LXR AGONIST AZ876 REDUCES ATHEROSCLEROSIS WITHOUT INCREASING TRIGLYCERIDES IN PLASMA AND LIVER J van der Hoorn, D Linden, M Bekkers, M Voskuilen, U Lindahl, J Oscarsson, E Lindstedt, H Princen TNO BioSciences, Leiden; AstraZeneca, Molndal Objectives Liver X receptor (LXR) agonists are atheroprotective, but may induce hypertriglyceridemia and liver steatosis. We investigated the effect of the new LXR agonist AZ876 (AZ) on plasma lipids, inflammation and atherosclerosis. GW3965 (GW) was used as a reference. Methods APOE*3Leiden mice were fed an atherogenic diet alone or supplemented with either AZ (5 or 20 μmol/kg) or GW (17 μmol/kg). Effects on plasma parameters and atherosclerosis were assessed after 20 weeks of treatment. Results As compared to control, low dose AZ had no effect on plasma lipids, whereas the high dose AZ increased plasma triglycerides (+150%; p<0.001) and reduced cholesterol (-16%; p<0.05). GW increased plasma triglycerides (+70%; p<0.001). Low dose AZ reduced lesion area (-47%, p<0.05); and high dose AZ strongly decreased lesion area (-91%), the number of lesions (-59%) and lesion severity. In either dose AZ did not affect lesion composition. GW significantly reduced atherosclerosis, but also tended to decrease lesion stability. The atheroprotective effect by high dose AZ and GW were partly explained by their antiinflammatory effects. As low dose AZ did not reduce inflammation markers, the induction of reverse cholesterol transport may be its primary protective action. Signs of liver steatosis were not observed by treatment with low dose AZ or GW. Conclusions We identified a novel LXR agonist that inhibits the progression of atherosclerosis presumably by increasing reverse cholesterol transport rather than by decreasing inflammation, without inducing detrimental lipogenic effects in liver and hypertriglyceridemia. Funding: AstraZeneca provided a grant." @default.
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- W1986381254 date "2009-06-01" @default.
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- W1986381254 title "Abstract: P482 NOVEL LXR AGONIST AZ876 REDUCES ATHEROSCLEROSIS WITHOUT INCREASING TRIGLYCERIDES IN PLASMA AND LIVER" @default.
- W1986381254 doi "https://doi.org/10.1016/s1567-5688(09)70777-9" @default.
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