Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca2 cycling proteinsReportar como inadecuado




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Journal of Translational Medicine

, 12:323

Nutrition and metabolism

Abstract

BackgroundCardiac 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 handling proteins.

MethodsTo 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 handling proteins were measured by western blot analysis.

ResultsHistological 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 HandE 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 handling proteins induced by aortic banding, including downregulation of sarcoplasmic reticulum Ca ATPase 2 SERCA2 and ryanodine receptor 2 RyR2, hypophosphorylated phospholamban PLB, upregulation of Na-Ca-exchangers NCX1 and increased expression and phosphorylation of Ca-calmodulin -dependent protein kinase II CaMKII. Moreover, resveratrol alleviated the decreased SERCA activity induced by aortic banding.

ConclusionsResveratrol 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 handling proteins.

KeywordsResveratrol Heart failure Hypertrophy Ultrastructure Ca2+ handling proteins AbbreviationsHFHeart failure

POPressure overload

SRSarcoplasmic reticulum

LVLeft ventricular

FSFractional shortening

EFEjection fraction

VmaxMaximal velocity through left ventricular outflow tract

LVIDd and LVIDsLV internal dimensions at both diastole and systole

LVPWd and LVPWsLV posterior wall dimensions at both diastole and systole

IVSd and IVSsInterventricular septal dimensions at both diastole and systole

LVm-BWLV mass-to-body weight ratio

TEMTransmission electron microscopy

CaMKIICa-calmodulin -dependent protein kinase II

p-CaMKIIPhospho-CaMKII Thr286

SERCA2Sarcoplasmic reticulum Ca ATPase 2

RyR2Ryanodine receptor 2

PLBPhospholamban

NCX1Na-Ca-exchangers

p-PLBPhospho-PLB S16

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-014-0323-x contains supplementary material, which is available to authorized users.

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Autor: Qi Dong - Zhiye Wu - Xiaoyun Li - Jianyun Yan - Luning Zhao - Chuntao Yang - Junjiang Lu - Ju Deng - Minsheng Chen

Fuente: https://link.springer.com/







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