Comparative study of effects of two LXR agonists on anti-atherosclerosis in ApoE-/-mice

Objective To investigate the effects of two types of liver X receptor (LXR) ligands/agonists T-0901317 and methyl 3β-hydroxy-5α, 6α-epoxycholanate (MHEC, synthesized by Third Military Medical University) on ApoE -/- mice (ApoE gene was knocked-out) and the major mechanisms. Methods ApoE -/- mice were divided into control group, MHEC group, and T-0901317 group (6 in each group). Mice in the interventional groups were orally administered with MHEC and T-0901317 at the dose of 10 mg·kg -1·d -1 consecutively for 6 weeks. Plasma lipids were determined by biochemical methods. The extents of atherosclerosis in the wall of aorta were measured by pathological method. The expressions of ATP-binding cassette transporter A1 (ABCA1) in the aortic atherosclerotic lesions in ApoE-/- mice were detected by immunohistochemical SP method. Results The contents of total cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) in T-0901317 group were significantly higher than those in the control group (P0.01), but only HDL-c in MHEC group was higher than that in the control group (P0.01). LXR agonists could significantly inhibit the development of atherosclerotic lesions in ApoE-/- mice (P0.01). Two LXR agonists could increase the expression of ABCA1 in the artery wall. Conclusion Two LXR agonists can inhibit the development of atherosclerotic lesions in ApoE-/- mice, but MHEC may have better effects on serum lipid than T-0901317, suggesting that LXR agonists could enhance the reverse cholesterol transport in vivo by upregulating ABCA1 expression in the aorta wall.