Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca2+ cycling proteins

Journal of Translational Medicine

Minsheng Chen¹  Ju Deng⁴  Junjiang Lu⁶  Chuntao Yang³  Luning Zhao²  Jianyun Yan¹  Xiaoyun Li⁴  Zhiye Wu¹  Qi Dong⁵ 

[1] Southern Medical University, 1838 Guang zhou da dao bei, Guangzhou 510515, China;Experimental Medical Research Center, Guangzhou Medical University, Guangzhou 510182, China;Department of Physiology, Guangzhou Medical University, Guangzhou 510182, China;Department of Cardiology, The Second Hospital Affiliated with Guangzhou Medical University, Guangzhou 510260, China;Guangzhou Institute of Cardiovascular Disease, Guangzhou 510260, China;Department of Neurology, The Fifth Hospital Affiliated with Zunyi Medical College, Zhuhai 519100, China

关键词: Ca2+ handling proteins;    Ultrastructure;    Hypertrophy;    Heart failure;    Resveratrol;   

Others  :  1147075
DOI  :  10.1186/s12967-014-0323-x

 received in 2014-09-04, accepted in 2014-11-10,  发布年份 2014

【 摘 要 】

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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ handling proteins induced by aortic banding, including downregulation of sarcoplasmic reticulum Ca²⁺ ATPase ₂ (SERCA₂) and ryanodine receptor ₂ (RyR₂), hypophosphorylated phospholamban (PLB), upregulation of Na⁺/Ca²⁺-exchangers (NCX₁) and increased expression and phosphorylation of Ca²⁺/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 Ca²⁺ handling proteins.

【 授权许可】

   
2014 Dong et al.; licensee BioMed Central Ltd.

【 图 表 】

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