首页    期刊浏览 2024年11月30日 星期六
登录注册

文章基本信息

  • 标题:Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice
  • 作者:Elyisha A. Hanniman ; Gilles Lambert ; Tanya C. McCarthy
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2005
  • 卷号:46
  • 期号:12
  • 页码:2595-2604
  • DOI:10.1194/jlr.M500390-JLR200
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要: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. This study was undertaken to investigate the pathological consequences of the loss of FXR function on the risk and severity of atherosclerosis. For this purpose, FXR-deficient ( 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 with wild-type, 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 aminotransferase), and increased inflammatory gene expression. Measurement of en face lesion area of HF/HC-challenged mice revealed that although FXR / mice did not develop atherosclerosis, FXR / ApoE / mice had approximately double the lesion area compared with 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.
Loading...
联系我们|关于我们|网站声明
国家哲学社会科学文献中心版权所有