title: Liver X receptor activation attenuates plaque formation and improves vasomotor function of the aortic artery in atherosclerotic ApoE(-/-) mice.
abstract: OBJECTIVE
  The severity of atherosclerosis is primarily determined by overall lipid metabolism and the degree of inflammation present within the vessel wall. We evaluated the effects of T-0901317, a liver X receptor agonist, on the atherosclerosis process, and especially on the endothelial function in ApoE(-/-) mice.
  
  
  RESULTS
  ApoE(-/-) mice were treated with LXR agonist T-0901317 (1 μmol/L) for 6 weeks. ApoE(-/-) mice receiving T-0901317 were found to have markedly improved overall serum lipid profiles, albeit increased serum triglycerides. MRI imaging demonstrated that T-0901317 attenuated the atherosclerotic plaque burden in the aorta of ApoE(-/-) mice. Transmission electron microscopy and immunohistochemistry revealed attenuated ultrastructural changes as well as enhanced expression of the ATP-binding cassette transporter ABCA1. In addition, treatment with the LXR agonist improved the vasomotor function of atherosclerotic arteries, as assessed by KCl/norepinephrine-induced vasoconstrictive and acetylcholine-induced vasorelaxation functional assays. In vitro studies showed increased ABCG1, phospho-Akt and phospho-eNOS expression in ApoE(-/-) mice aorta endothelial cells (ECs) after T0901317 treatment.
  
  
  CONCLUSIONS
  The present study suggest that LXR agonists protect the endothelium against atherosclerotic insults by increasing ABCA1 and ABCG1 expression, and improve the endothelial-dependent vasomotor function probably by promoting Akt and eNOS phosphorylation.
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
authors: Jianghong
authors: J
authors: Chen
authors: Li
authors: L
authors: Zhao
authors: Dongdong
authors: D
authors: Sun
authors: Kazim
authors: K
authors: Narsinh
authors: Chunhong
authors: C
authors: Li
authors: Zheng
authors: Z
authors: Zhang
authors: Shun
authors: S
authors: Qi
authors: Guangquan
authors: G
authors: Wei
authors: Weijie
authors: W
authors: Li
authors: Wenyi
authors: W
authors: Guo
authors: Feng
authors: F
authors: Cao
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D006845:Hydrocarbons, Fluorinated; D008055:Lipids; D008074:Lipoproteins; D000071518:Liver X Receptors; D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C487540:ABCG1 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C496315:Nos3 protein, mouse