title: Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca(2+) cycling proteins.
abstract: BACKGROUND
  Cardiac hypertrophy is a compensatory stage of the heart in response to stress such as pressure overload (PO), which can develop into heart failure (HF) if left untreated. Resveratrol has been reported to prevent the development of hypertrophy and contractile dysfunction induced by PO. However, other studies found that resveratrol treatment for a longer period of time failed to regress cardiac hypertrophy. The aim of this study is to determine the timing of resveratrol treatment to achieve antihypertrophic effect and investigate whether resveratrol prevents the development of HF through preservation of myocardium structure and modulation of Ca(2+) handling proteins.
  
  
  METHODS
  To generate rats with cardiac hypertrophy, male Sprague-Dawley rats were subjected to PO (aortic banding procedure) for 4 weeks. Sham-operated animals served as controls. Rats with cardiac hypertrophy were given resveratrol (4 mg/kg/day) for 4, 6, and 8 weeks, respectively. Histological and echocardiographic analysis and transmission electron microscopy were performed to assess cardiac structure and function. The levels of Ca(2+) handling proteins were measured by western blot analysis.
  
  
  RESULTS
  Histological analysis showed that resveratrol treatment regressed developed cardiac hypertrophy at 8 and 10 weeks postsurgery, but not at 12 weeks. However, resveratrol strongly and continuously prevented the development of cardiac dysfunction and dilation of cardiac chamber as evaluated by echocardiography and H&E staining of heart cross-sections. In addition, PO-induced cardiac fibrosis was completely inhibited by resveratrol treatment. Resveratrol markedly prevented the disrupted myocardium but partially rescued mitochondrial abnormality in banded rats. Moreover, resveratrol prevented the alteration of Ca(2+) handling proteins induced by aortic banding, including downregulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and ryanodine receptor 2 (RyR2), hypophosphorylated phospholamban (PLB), upregulation of Na(+)/Ca(2+)-exchangers (NCX1) and increased expression and phosphorylation of Ca(2+)/calmodulin -dependent protein kinase II (CaMKII). Moreover, resveratrol alleviated the decreased SERCA activity induced by aortic banding.
  
  
  CONCLUSIONS
  Resveratrol effectively prevented the transition from compensatory to decompensatory stage of cardiac hypertrophy induced by PO, but this effect is dependent on the timing of treatment. We suggest that resveratrol may exert beneficial effects on cardiac hypertrophy through protection of cardiac structure and modulation of Ca(2+) handling proteins.
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, China. dongqistar@hotmail.com.|Guangzhou Institute of Cardiovascular Disease, Guangzhou, 510260, China. dongqistar@hotmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Guangzhou, 510260, China. 401145400@qq.com.|Southern Medical University, 1838 Guang zhou da dao bei, Guangzhou, 510515, China. 401145400@qq.com.
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The Second Hospital Affiliated with Guangzhou Medical University, Guangzhou, 510260, China. yun530@sohu.com.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Li
authors.affiliation: Southern Medical University, 1838 Guang zhou da dao bei, Guangzhou, 510515, China. yanjy790@163.com.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Experimental Medical Research Center, Guangzhou Medical University, Guangzhou, 510182, China. zhao.luning@yahoo.com.cn.
authors.forename: Luning
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, China. yang-chuntao@163.com.
authors.forename: Chuntao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Neurology, The Fifth Hospital Affiliated with Zunyi Medical College, Zhuhai, 519100, China. lujinjiang1107@126.com.
authors.forename: Junjiang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Guangzhou, 510260, China. dengju520@foxmail.com.|Department of Cardiology, The Second Hospital Affiliated with Guangzhou Medical University, Guangzhou, 510260, China. dengju520@foxmail.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Deng
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Guangzhou, 510260, China. min_sheng_chen@hotmail.com.|Southern Medical University, 1838 Guang zhou da dao bei, Guangzhou, 510515, China. min_sheng_chen@hotmail.com.
authors.forename: Minsheng
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol; D002118:Calcium