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

Abstract

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.

DOI: 10.1016/j.ijcard.2016.04.007

Cite this paper

@article{Wang2016CandesartanCA, title={Candesartan cilexetil attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR.}, author={Zuoguang Wang and Qiuli Niu and Xiaoyun Peng and Mei Li and Kuo Liu and Ya Liu and Jielin Liu and Fei Jin and Xiao Fan Li and Yongxiang Wei}, journal={International journal of cardiology}, year={2016}, volume={214}, pages={348-57} }