Our studies and others recently demonstrate that polydatin, a resveratrol glucoside, has antioxidative and cardioprotective effects. This study aims to investigate the direct effects of polydatin on Ang II-induced cardiac hypertrophy to explore the potential role of polydatin in cardioprotection. Our results showed that in primary cultured cardiomyocytes, polydatin blocked Ang II-induced cardiac hypertrophy in a dose-dependent manner, which were associated with reduction in the cell surface area and [3H]leucine incorporation, as well as attenuation of the mRNA expressions of atrial natriuretic factor and β-myosin heavy chain. Furthermore, polydatin prevented rat cardiac hypertrophy induced by Ang II infusion, as assessed by heart weight-to-body weight ratio, cross-sectional area of cardiomyocyte, and gene expression of hypertrophic markers. Further investigation demonstrated that polydatin attenuated the Ang II-induced increase in the reactive oxygen species levels and NADPH oxidase activity in vivo and in vitro. Polydatin also blocked the Ang II-stimulated increases of Nox4 and Nox2 expression in cultured cardiomyocytes and the hearts of Ang II-infused rats. Our results indicate that polydatin has the potential to protect against Ang II-mediated cardiac hypertrophy through suppression of NADPH oxidase activity and superoxide production. These observations may shed new light on the understanding of the cardioprotective effect of polydatin.
KoitabashiNKassDA. Reverse remodeling in heart failure – mechanisms and therapeutic opportunities. Nat Rev Cardiol2011; 9: 147–57.
2.
MaytinMColucciWS. Molecular and cellular mechanisms of myocardial remodeling. J Nucl Cardiol2002; 9: 319–27.
3.
KimSIwaoH. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev2000; 52: 11–34.
4.
MehtaPKGriendlingKK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol2007; 292: C82–97.
5.
AinscoughJFDrinkhillMJSedoATurnerNABrookeDABalmforthAJBallSG. Angiotensin II type-1 receptor activation in the adult heart causes blood pressure-independent hypertrophy and cardiac dysfunction. Cardiovasc Res2009; 81: 592–600.
6.
RosenkranzS. TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res2004; 63: 423–32.
7.
DasguptaCZhangL. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discov Today2011; 16: 22–34.
8.
KurdiMBoozGW. New take on the role of angiotensin II in cardiac hypertrophy and fibrosis. Hypertension2011; 57: 1034–8.
9.
MaejimaYKurodaJMatsushimaSAgoTSadoshimaJ. Regulation of myocardial growth and death by NADPH oxidase. J Mol Cell Cardiol2011; 50: 408–16.
10.
BendallJKCaveACHeymesCGallNShahAM. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation2002; 105: 293–6.
11.
PimentelDRAminJKXiaoLMillerTViereckJOliver-KrasinskiJBaligaRWangJSiwikDASinghKPaganoPColucciWSSawyerDB. Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res2001; 89: 453–60.
12.
HayashiDKudohSShiojiamaIZouYHaradaKShimoyamaMImaiYMonzenKYamazakiTYazakiYNagaiRKomuroI. Atrial natriuretic peptide inhibits cardiomyocyte hypertrophy through mito-geneactivated protein kinase phosphatase-1. Biochem Biophys Res Commun2004; 322: 310–9.
13.
PapparellaICeolottoGMontemurroDAntonelloMGarbisaSRossiGSempliciniA. Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by modulating reactive oxygen species production and the Src/epidermal growth factor receptor/Akt signaling pathway. J Nutr2008; 138: 1596–601.
14.
DongJWangHWanLHashiYChenS. Identification and determination of major constituents in Polygonum cuspidatum Sieb. et Zucc. by high performance liquid chromatography/electrospray ionization-ion trap-time-of-flight mass spectrometry. Se Pu2009; 27: 425–30.
15.
LiuLTGuoGWuMZhangWG. The progress of the research on cardio-vascular effects and acting mechanism of polydatin. Chin J Integr Med2012; 18: 714–9.
16.
GoldbergDMEric NgAKDiamandisEPSoleasGJ. Resveratrol glucosides are important components of commercial wines. Am J Enol Vitic1996; 47: 415–20.
17.
LanzilliGCottarelliANicoteraGGuidaSRavagnanGFuggettaMP. Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation2012; 35: 240–8.
18.
ZhangJTanYYaoFZhangQ. Polydatin alleviates non-alcoholic fatty liver disease in rats by inhibiting the expression of TNF-α and SREBP-1c. Mol Med Rep2012; 6: 815–20.
MiaoQWangSMiaoSWangJXieYYangQ. Cardioprotective effect of polydatin against ischemia/reperfusion injury: roles of protein kinase C and mito KATP activation. Phytomedicine2011; 19: 8–12.
21.
GaoJPChenCXGuWLWuQWangYLuJ. Effects of polydatin on attenuating ventricular remodeling in isoproterenol-induced mouse and pressure-overload rat models. Fitoterapia2010; 81: 953–60.
22.
ZhangLPYangCYWangYPCuiFZhangY. Protective effect of polydatin against ischemia/reperfusion injury in rat heart. Sheng Li Xue Bao2008; 60: 161–8.
23.
DengJLiuWWangYDongMZhengMLiuJ. Polydatin modulates Ca(2+) handling, excitation-contraction coupling and β-adrenergic signaling in rat ventricular myocytes. J Mol Cell Cardiol2012; 53: 646–56.
24.
JiangXLiuWDengJLanLXueXZhangCCaiGLuoXLiuJ. Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors. Free Radic Biol Med2013; 60: 292–9.
25.
XuanCLYaoFRGuoLRLiuQChangSKLiuKXSunCW. Comparison of extracts from cooked and raw lentil in antagonizing angiotensin II-induced hypertension and cardiac hypertrophy. Eur Rev Med Pharmacol Sci2013; 17: 2644–53.
26.
HuCMChenYHChiangMTChauLY. Heme oxygenase-1 inhibits angiotensin II-induced cardiac hypertrophy in vitro and in vivo. Circulation2004; 110: 309–16.
27.
ZhangQYaoFRaizadaMKO'RourkeSTSunC. Apelin gene transfer into the rostral ventrolateral medulla induces chronic blood pressure elevation in normotensive rats. Circ Res2009; 104: 1421–8.
28.
HwangSYSiowYLAu-YeungKKHouseJOK. Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney. Am J Physiol Renal Physiol2011; 300: F189–98.
29.
SchlüterKDWenzelS. Angiotensin II: a hormone involved in and contributing to pro-hypertrophic cardiac networks and target of anti-hypertrophic cross-talks. Pharmacol Ther2008; 119: 311–25.
30.
GarridoAMGriendlingKK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol2009; 302: 148–58.
31.
SirkerAZhangMMurdochCShahAM. Involvement of NADPH oxidases in cardiac remodelling and heart failure. Am J Nephrol2007; 27: 649–60.
32.
ByrneJAGrieveDJBendallJKLiJMGoveCLambethJDCaveACShahAM. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res2003; 93: 802–5.
33.
SatohMOgitaHTakeshitaKMukaiYKwiatkowskiDJLiaoJK. Requirement of Rac1 in the development of cardiac hypertrophy. Proc Natl Sci U S A2006; 103: 7432–7.
34.
KurodaJAgoTMatsushimaSZhaiPSchneiderMDSadoshimaJ. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A2010; 107: 15565–70.
35.
AgoTKurodaJPainJFuCLiHSadoshimaJ. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res2010; 106: 1253–64.
36.
MaejimaYKurodaJMatsushimaSAgoTSadoshimaJ. Regulation of myocardial growth and death by NADPH oxidase. J Mol Cell Cardiol2011; 50: 408–16.
37.
HingtgenSDTianXYangJDunlaySMPeekASWuYSharmaRVEngelhardtJFDavissonRL. Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin II-induced cardiomyocyte hypertrophy. Physiol Genomics2006; 26: 180–91.
