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 Ca2+ 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 Ca2+ 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 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.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 Ca2+ handling proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0323-x) contains supplementary material, which is available to authorized users.
Highlights
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
LVIDs was significantly decreased in aortic banded rats compared with sham rats, whereas no significant difference in LVIDd was detected between the two groups (Additional file 1C)
Antihypertrophic effect of resveratrol Histological analysis showed that surface areas and diameters of cardiomyocytes were remarkably increased at 8, 10 and 12 weeks postsurgery in aortic banded rats compared with sham rats, but decreased by 27%, 14% at 8 weeks and 46%, 26% at 10 weeks postsurgery respectively in resveratrol-treated rats compared to banded rats
Summary
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. The initial phase is beneficial in maintaining cardiac function, prolonged hypertrophy will lead to deleterious consequences and eventually HF. Nowadays, many medicines, such as β-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensinreceptor blockers and diuretics, have been universally used to treat cardiac hypertrophy and HF. Many medicines, such as β-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensinreceptor blockers and diuretics, have been universally used to treat cardiac hypertrophy and HF These medicines can be effective to partially relieve the symptoms of HF, but cannot reverse the progression of HF.
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