Effect of liver X-receptor agonist on atherosclerosis of apolipoprotein E-deficient mice

AIM: To observe the effects and mechanisms of liver X-receptor (LXR) agonist (T-0901317) on aorta structure, blood vessel activity and atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Twelve-week-old ApoE-/- mice were divided randomly into model group (fed with saline, AS) and LXR agonist group (fed with LXR agonist, AS+L), and normal C57BL/6J mice were randomized into control group (fed with saline, C) and singlet intervention group (fed with LXR agonist, L). LXR agonist (T-0901317) was orally administered daily at a dose of 10 mg/kg for 6 weeks. Plasma lipids were determined after 6 weeks treatment. Aortas were isolated and observed by transmission electron microscopy and expressions of ATP-binding cassette transporter A1 (ABCA1) in the aortic atherosclerotic lesions were detected by Western blot method. RESULTS: Levels of total cholesterol, triglyceride and high-density lipoprotein cholesterol in AS+L group were significantly lower than those in AS group (P<0.05). LXR agonist inhibited degeneration and necrosis of endothelium and significantly reversed the development of atherosclerotic lesions compared with that in AS group. Expressions of ABCA1 in the artery wall were elevated in AS+L group compared with those in AS control. CONCLUSION: LXR agonist significantly decreases the level of serum lipids and reverses the development of atherosclerotic lesions in ApoE-/- mice. It is suggested that LXR agonist has favorable effects on artery endothelium repair, possibly by enhancing the reverse cholesterol transport in vivo via upregulating ABCA1 expression within the aorta wall.