title: 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.
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China. Electronic address: wzg70@hotmail.com.
authors.forename: Zuoguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Niu
authors.affiliation: Institute of Westnorth Plateau Biology, Chinese Academy of Sciences, 650032, PR China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Jielin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing 100029, PR China. Electronic address: wyhhzq818@sina.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D020558:GTP Phosphohydrolases; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D013777:Tetrazoles; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C077793:candesartan cilexetil
keywords: Antihypertensive treatment; Cardiac remodeling; Mitochondria; Mitofusin 2; Oxidative stress