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Candesartan cilexetil attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR.

Authors: Wang, Zuoguang  Niu, Qiuli  Peng, Xiaoyun  Li, Mei  Liu, Kuo  Liu, Ya  Liu, Jielin  Jin, Fei  Li, Xiao  Wei, Yongxiang 
Citation: Wang Z, etal., Int J Cardiol. 2016 Jul 1;214:348-57. doi: 10.1016/j.ijcard.2016.04.007. Epub 2016 Apr 5.
Pubmed: (View Article at PubMed) PMID:27085127
DOI: Full-text: DOI:10.1016/j.ijcard.2016.04.007

BACKGROUND: Left ventricular hypotrophy (LVH) is very common in hypertensives even after antihypertensive treatment. Mitofusin 2 (Mfn2) is a critical negative regulator of vascular smooth muscle cell (VSMC) hypertrophy by regulating mitochondrial fusion, ras/raf/MEK signal pathway, et al. The purpose of this study was to investigate whether candesartan attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR.
METHODS: Nine weeks old spontaneously hypertensive rats (SHR) were selected and treated with candesartan for eight weeks. Then, heart tissues were investigated for signs of cardiac remodeling, mitochondrial structure and membrane potential, mitochondrial enzyme activities, hydrogen peroxide, mRNA and protein expression of Mfn2/ras/raf/MEK signaling pathway in heart tissues.
RESULTS: The results showed that cardiac remodeling was obviously in SHR group: cardiac cell alignment was irregular; cardiac fibers became thick, irregular and enlarged; cell density was reduced in SHR compared to WKY. After candesartan treatment, histopathological structure improved significantly which were consistent with mitochondrial morphology, mitochondrial membrane potential, mitochondrial enzyme activities, hydrogen peroxide, Mfn2/ras/raf/MEK gene and protein expression in cardiac tissues. What's more, although blood pressure was well controlled in a normal range, cardiac remodeling wasn't avoided. In general, candesartan obviously repressed cardiac hypertrophy and cardiac remodeling significantly compared to SHR untreated group, but didn't reverse it.
CONCLUSIONS: Mfn2 is negatively associated with cardiac remodeling. Candesartan treatment can improve mitochondrial structure and function and regulate Mfn2/ras/raf/MEK signaling pathway. Mfn2 may be used a potential marker for cardiac remodeling and a novel therapeutic target for target organ damage protection.


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CRRD Object Information
CRRD ID: 12910835
Created: 2017-06-26
Species: All species
Last Modified: 2017-06-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.