Article
Lipogenesis in arterial wall and vascular smooth muscle cells of Psammomys obesus: its regulation and abnormalities in diabetes.
ERI22-EA4173, faculté Rockefeller, UCB Lyon 1, 8, avenue Rockfeller, 69008 Lyon, France.
Diabetes & Metabolism (impact factor:
2.41).
03/2010;
36(3):221-8.
DOI:10.1016/j.diabet.2010.01.003
Source: PubMed
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Citations (0)
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Article: Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress.
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ABSTRACT: Circulating endogenous, dietary, and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene programme in the vasculature. PXR was detected in primary human and rat aortic endothelial and smooth muscle cells (SMC) and blood vessels including the human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C, and glutathione S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR-null mice stimulated in vivo or in rat aortic SMC expressing dominant-negative PXR. Activation of aortic PXR by classical agonists had several protective effects: increased xenobiotic metabolism demonstrated by bioactivation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death. PXR co-ordinately up-regulates drug metabolism, transport, and antioxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence.Cardiovascular research 12/2011; 93(4):674-81. · 5.80 Impact Factor
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Keywords
ACC1 expression
arterial wall
cholesterol esterification
clear stimulatory action
diabetic animals
diabetic animals exhibited lipid deposits
fatty acids
high-fat diet
histological examination
lipid accumulation
lipogenic gene expression
LXR agonists
moderate effect
non-diabetic animals
non-diabetic P. obesus
P. obesus
Psammomys obesus gerbils
situ lipogenesis
stimulatory action
VSMC culture