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Inflamm Res. 2012 Dec;61(12):1299-307. doi: 10.1007/s00011-012-0529-4. Epub 2012 Jul 26.

Liver X receptor activation attenuates plaque formation and improves vasomotor function of the aortic artery in atherosclerotic ApoE(-/-) mice.

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  • 1Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.

Abstract

AIM:

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.

METHODS AND 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.

CONCLUSION:

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.

[PubMed - indexed for MEDLINE]
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