期刊
KIDNEY INTERNATIONAL
卷 75, 期 8, 页码 800-808出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2008.690
关键词
blood pressure; rapamycin; uremia; ventricular hypertrophy
资金
- Burroughs Wellcome Fund
- NIH grants [RO1 HL061567, P01 HL057278, RO1 HL 076670, P30 DK079333]
- DDRCC Morphology Core Facility at Washington University [NIH DDRCC P30 DK52574]
Chronic kidney disease is often complicated by uremic cardiomyopathy that consists of left ventricular hypertrophy and interstitial fibrosis. It is thought that hypertension and volume overload are major causes of this disease, but here we sought to identify additional mechanisms using a mouse model of chronic renal insufficiency. Mice with a remnant kidney developed an elevated blood urea nitrogen by 1 week, as expected, and showed progressive cardiac hypertrophy and fibrosis at 4 and 8 weeks even though their blood pressures were not elevated nor did they show signs of volume overload. Cardiac extracellular signal-regulated kinase (ERK) was activated in the uremic animals at 8 weeks. There was also an increased phosphorylation of S6 kinase, which is often mediated by activation of the mammalian target of rapamycin (mTOR). To test the involvement of this pathway, we treated these uremic mice with rapamycin and found that it reduced cardiac hypertrophy. Reduction of blood pressure, however, by hydralazine had no effect. These studies suggest that uremic cardiomyopathy is mediated by activation of a pathway that involves the mTOR pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据