|
A more recent version of this article appeared on December 1, 2005
Papers In Press, published online ahead of print September 26, 2005
J. Lipid Res., doi:10.1194/jlr.M500390-JLR200
Submitted on August 29, 2005
Revised on September 15, 2005
Accepted on September 26, 2005
Loss of functional farnesoid X-receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice
Elyisha A. Hanniman, Gilles Lambert, Tanya C. McCarthy, and Christopher J. Sinal
Pharmacology Dept., Dalhousie University, Halifax, Nova Scotia B3H 1X5
Corresponding Author: csinal{at}dal.ca
The farnesoid X receptor (FXR) is a bile acid-activated transcription factor that regulates the expression of genes critical for bile acid and lipid homeostasis. The present study was undertaken to investigate the pathological consequences of loss of FXR function on the risk and severity of atherosclerosis. For this purpose, FXR/ mice were crossed with apolipoprotein E-deficient (ApoE/) mice to generate FXR/ApoE/ mice. Challenging these mice with a high fat, high cholesterol (HF/HC) diet resulted in reduced weight gain and decreased survival compared to wildtype, FXR/ and ApoE/ mice. FXR/ApoE/ mice also had the highest total plasma lipids and the most atherogenic lipoprotein profile. Livers from FXR/ and FXR/ApoE/ mice exhibited marked lipid accumulation, focal necrosis accompanied by increased levels of plasma aspartate amino transferase and increased inflammatory gene expression. Measurement of en face lesion area of HF/HC challenged mice revealed that while FXR/ mice did not develop atherosclerosis, FXR/ApoE/ mice had approximately double the lesion area compared to ApoE/ mice. In conclusion, loss of FXR function is associated with decreased survival, increased severity of defects in lipid metabolism and more extensive aortic plaque formation in a mouse model of atherosclerotic disease.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
X. X. Wang, T. Jiang, Y. Shen, L. Adorini, M. Pruzanski, F. J. Gonzalez, P. Scherzer, L. Lewis, S. Miyazaki-Anzai, and M. Levi
The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria
Am J Physiol Renal Physiol,
December 1, 2009;
297(6):
F1587 - F1596.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. B. Hartman, S. J. Gardell, C. J. Petucci, S. Wang, J. A. Krueger, and M. J. Evans
Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice
J. Lipid Res.,
June 1, 2009;
50(6):
1090 - 1100.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. B. Hartman, K. Lai, and M. J. Evans
Loss of small heterodimer partner expression in the liver protects against dyslipidemia
J. Lipid Res.,
February 1, 2009;
50(2):
193 - 203.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Mencarelli, B. Renga, E. Distrutti, and S. Fiorucci
Antiatherosclerotic effect of farnesoid X receptor
Am J Physiol Heart Circ Physiol,
February 1, 2009;
296(2):
H272 - H281.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Kong, J. P. Luyendyk, O. Tawfik, and G. L. Guo
Farnesoid X Receptor Deficiency Induces Nonalcoholic Steatohepatitis in Low-Density Lipoprotein Receptor-Knockout Mice Fed a High-Fat Diet
J. Pharmacol. Exp. Ther.,
January 1, 2009;
328(1):
116 - 122.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Zhang, F. He, R. Kuruba, X. Gao, A. Wilson, J. Li, T. R. Billiar, B. R. Pitt, W. Xie, and S. Li
FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells
Cardiovasc Res,
February 1, 2008;
77(3):
560 - 569.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. T.Y. Li, K. E. Swales, G. J. Thomas, T. D. Warner, and D. Bishop-Bailey
Farnesoid X Receptor Ligands Inhibit Vascular Smooth Muscle Cell Inflammation and Migration
Arterioscler Thromb Vasc Biol,
December 1, 2007;
27(12):
2606 - 2611.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. A. Hanniman, G. Lambert, Y. Inoue, F. J. Gonzalez, and C. J. Sinal
Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4{alpha}, and PGC-1{alpha}
J. Lipid Res.,
November 1, 2006;
47(11):
2503 - 2514.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zhang, X. Wang, C. Vales, F. Y. Lee, H. Lee, A. J. Lusis, and P. A. Edwards
FXR Deficiency Causes Reduced Atherosclerosis in Ldlr-/- Mice
Arterioscler Thromb Vasc Biol,
October 1, 2006;
26(10):
2316 - 2321.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Caron, B. Cariou, and B. Staels
FXR: More than a Bile Acid Receptor?
Endocrinology,
September 1, 2006;
147(9):
4022 - 4024.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Wang, K. Lai, F. J. Moy, A. Bhat, H. B. Hartman, and M. J. Evans
The Nuclear Hormone Receptor Farnesoid X Receptor (FXR) Is Activated by Androsterone
Endocrinology,
September 1, 2006;
147(9):
4025 - 4033.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|