Constitutive androstane receptor activation decreases plasma apolipoprotein B-containing lipoproteins and atherosclerosis in low-density lipoprotein receptor-deficient mice.
Arterioscler Thromb Vasc Biol
; 31(10): 2232-9, 2011 Oct.
Article
in En
| MEDLINE
| ID: mdl-21778422
ABSTRACT
OBJECTIVE:
The goal of this study was to determine the impact of the nuclear receptor constitutive androstane receptor (CAR) on lipoprotein metabolism and atherosclerosis in hyperlipidemic mice. METHODS ANDRESULTS:
Low-density lipoprotein receptor-deficient (Ldlr(-/-)) and apolipoprotein E-deficient (ApoE(-/-)) mice fed a Western-type diet were treated weekly with the Car agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or the vehicle only for 8 weeks. In Ldlr(-/-) mice, treatment with TCPOBOP induced a decrease in plasma triglyceride and intermediate-density lipoprotein/low-density lipoprotein cholesterol levels (≈30% decrease in both cases after 2 months, P<0.01). These mice also showed a significant reduction in the production of very-low-density lipoproteins associated with a decrease in hepatic triglyceride content and the repression of several genes involved in lipogenesis. TCPOBOP treatment also induced a marked increase in the very-low-density lipoprotein receptor in the liver, which probably contributed to the decrease in intermediate-density lipoprotein/low-density lipoprotein levels. Atherosclerotic lesions in the aortic valves of TCPOBOP-treated Ldlr(-/-) mice were also reduced (-60%, P<0.001). In ApoE(-/-) mice, which lack the physiological apoE ligand for the very-low-density lipoprotein receptor, the effect of TCPOBOP on plasma cholesterol levels and the development of atherosclerotic lesions was markedly attenuated.CONCLUSIONS:
CAR is a potential target in the prevention and treatment of hypercholesterolemia and atherosclerosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins B
/
Pyridines
/
Receptors, LDL
/
Receptors, Cytoplasmic and Nuclear
/
Atherosclerosis
/
Hyperlipidemias
Type of study:
Prognostic_studies
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Journal subject:
ANGIOLOGIA
Year:
2011
Document type:
Article
Affiliation country: