Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep39186
Keywords
-
Categories
Funding
- National Natural Sciences Foundation of China [81170242, 81371571, 81400295]
- Research Fund of the Health Agency of Zhejiang Province [2014KYB099, 2016KYB100]
- Zhejiang Provincial Natural Science Foundation of China [LQ14H020004]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y200907825]
Ask authors/readers for more resources
Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous studies, we find that inhibition of FPPS attenuates angiotensin II-induced cardiac hypertrophy and fibrosis by suppressing RhoA while FPPS and Ras are up-regulated in pressure overload rats. In this study, we evaluate the effects and mechanisms of FPPS inhibition in pressure overload mice. Male FPPS-small interfering RNA (SiRNA) transgenic (Tg) mice and non-transgenic littermate control (NLC) were randomly divided into suprarenal abdominal aortic constriction (AAC) group and sham operation group. 12 weeks following AAC, mice were sacrificed by cervical dislocation. Histological and echocardiographic assessments showed that inhibition of FPPS improved chronic cardiac remodeling which was induced by AAC. The reductions of Ras farnesylation and GTP-Ras, as well as their downstream extracellular signal-related kinases 1/2 (ERK1/2) expression were observed in the heart of Tg-AAC mice compared with NLC-AAC mice, along with the reduction of fetal gene expression. We provide here important experimental evidence that inhibition of FPPS improves AAC induced chronic cardiac remodeling and fibrosis by the reduction of farnesylated Ras and the downregulation of Ras-ERK1/2 pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available