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Abstract: heart failure (HF) represents the most common endpoint of most cardiovascular diseases (CVDs) which are the leading causes of death around the world. Despite the advances in treating CVDs, the prevalence of HF continues to increase. It is believed that better results of prognosis are obtained from prevention rather than additional treatment for HF. Therefore, it is reasonable to prevent the development of CVDs or other complications to HF. Most types of HF are attributed to contractile dysfunction, cardiac hypertrophy or remodeling, and ischemic injuries. SIRT3 is a mitochondrial nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase whose substrates vary from metabolic biogenesis-associated proteins to stress-responsive proteins. In recent years, a number of studies have highlighted the cardio-protective role of SIRT3 and, as such, efforts have been made to induce over-expression or increased activity of this protein. In this review, we provide an overview of the roles of SIRT3 in cardiac hypertrophy induced by pressure overload or agonists and cardiomyocytes ischemic injuries. Moreover, we will introduce the application of SIRT3 agonists in the prevention of cardiac hypertrophy and ischemia reperfusion injury.

SIRT3在心衰中的作用：从基础到临床

[1]Adiga, I.K., Nair, R.R., 2008. Multiple signaling pathways coordinately mediate reactive oxygen species dependent cardiomyocyte hypertrophy. Cell Biochem. Funct., 26(3):346-351.

[2]Ahn, B.H., Kim, H.S., Song, S., et al., 2008. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS, 105(38):14447-14452.

[3]Al-Ahmad, A., Sarnak, M.J., Salem, D.N., 2001. Cause and management of heart failure in patients with chronic renal disease. Semin. Nephrol., 21(1):3-12.

[4]Bellizzi, D., Rose, G., Cavalcante, P., et al., 2005. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics, 85(2):258-263.

[5]Berndt, C., Lillig, C.H., Holmgren, A., 2007. Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system. Am. J. Physiol. Heart Circ. Physiol., 292(3):H1227-H1236.

[6]Bing, R.J., Siegel, A., Ungar, I., et al., 1954. Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. Am. J. Med., 16(4):504-515.

[7]Bochaton, T., Crola-Da-Silva, C., Pillot, B., et al., 2015. Inhibition of myocardial reperfusion injury by ischemic postconditioning requires sirtuin 3-mediated deacetylation of cyclophilin D. J. Mol. Cell. Cardiol., 84:61-69.

[8]Borbely, A., van der Velden, J., Papp, Z., et al., 2005. Cardiomyocyte stiffness in diastolic heart failure. Circulation, 111(6):774-781.

[9]Braunwald, E., 2013. Heart failure. JACC Heart Fail, 1(1):1-20.

[10]Briasoulis, A., Androulakis, E., Christophides, T., et al., 2016. The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure. Heart Fail Rev., 21(2):169-176.

[11]Cai, J., Yi, F.F., Bian, Z.Y., et al., 2009. Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway. J. Cell. Mol. Med., 13(5):909-925.

[12]Chen, C.J., Fu, Y.C., Yu, W., et al., 2013. SIRT3 protects cardiomyocytes from oxidative stress-mediated cell death by activating NF-κB. Biochem. Biophys. Res. Commun., 430(2):798-803.

[13]Chen, J., Normand, S.L., Wang, Y., et al., 2011. National and regional trends in heart failure hospitalization and mortality rates for medicare beneficiaries, 1998-2008. JAMA, 306(15):1669-1678.

[14]Chen, T., Li, J., Liu, J., et al., 2015a. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway. Am. J. Physiol. Heart Circ. Physiol., 308(5):H424-H434.

[15]Chen, T., Liu, J., Li, N., et al., 2015b. Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD. PLOS ONE, 10(3):e0118909.

[16]Cole, M.P., Chaiswing, L., Oberley, T.D., et al., 2006. The protective roles of nitric oxide and superoxide dismutase in adriamycin-induced cardiotoxicity. Cardiovasc. Res., 69(1):186-197.

[17]Daitoku, H., Hatta, M., Matsuzaki, H., et al., 2004. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. PNAS, 101(27):10042-10047.

[18]Dittenhafer-Reed, K.E., Richards, A.L., Fan, J., et al., 2015. SIRT3 mediates multi-tissue coupling for metabolic fuel switching. Cell Metab., 21(4):637-646.

[19]Eckner, R., 1996. p300 and CBP as transcriptional regulators and targets of oncogenic events. Biol. Chem., 377(11):685-688.

[20]Finkel, T., Deng, C.X., Mostoslavsky, R., 2009. Recent progress in the biology and physiology of sirtuins. Nature, 460(7255):587-591.

[21]Gandhi, M.S., Kamalov, G., Shahbaz, A.U., et al., 2011. Cellular and molecular pathways to myocardial necrosis and replacement fibrosis. Heart Fail. Rev., 16(1):23-34.

[22]Greco, C., Rosato, S., D'Errigo, P., et al., 2015. Trends in mortality and heart failure after acute myocardial infarction in Italy from 2001 to 2011. Int. J. Cardiol., 184:115-121.

[23]Guo, J., Gertsberg, Z., Ozgen, N., et al., 2009. p66Shc links α₁-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes. Circ. Res., 104(5):660-669.

[24]Hafner, A.V., Dai, J., Gomes, A.P., et al., 2010. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY), 2(12):914-923.

[25]Hannink, J.D., van Helvoort, H.A., Dekhuijzen, P.N., et al., 2010. Heart failure and COPD: partners in crime? Respirology, 15(6):895-901.

[26]Herman, D.S., Lam, L., Taylor, M.R., et al., 2012. Truncations of titin causing dilated cardiomyopathy. N. Engl. J. Med., 366(7):619-628.

[27]Hirschey, M.D., Shimazu, T., Goetzman, E., et al., 2010. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 464(7285):121-125.

[28]Hu, T.P., Xu, F.P., Li, Y.J., et al., 2006. Simvastatin inhibits leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes. Acta Pharmacol. Sin., 27(4):419-422.

[29]Hu, X.Q., Cheng, J., Tang, B., et al., 2014. Clinical effect of postconditioning in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 12(8):629-632.

[30]Hung, J., Teng, T.H., Finn, J., et al., 2013. Trends from 1996 to 2007 in incidence and mortality outcomes of heart failure after acute myocardial infarction: a population-based study of 20 812 patients with first acute myocardial infarction in Western Australia. J. Am. Heart Assoc., 2(5):e000172.

[31]Kamalesh, M., 2007. Heart failure in diabetes and related conditions. J. Card. Fail., 13(10):861-873.

[32]Katz, A.M., Zile, M.R., 2006. New molecular mechanism in diastolic heart failure. Circulation, 113(16):1922-1925.

[33]Kim, H.S., Patel, K., Muldoon-Jacobs, K., et al., 2010. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell, 17(1):41-52.

[34]Klishadi, M.S., Zarei, F., Hejazian, S.H., et al., 2015. Losartan protects the heart against ischemia reperfusion injury: sirtuin3 involvement. J. Pharm. Pharm. Sci., 18(1):112-123.

[35]Kober, L., 2016. Heart failure in 2015: better results from prevention than from additional treatment. Nat. Rev. Cardiol., 13(2):75-77.

[36]Koentges, C., Pfeil, K., Schnick, T., et al., 2015. SIRT3 deficiency impairs mitochondrial and contractile function in the heart. Basic Res. Cardiol., 110(4):36.

[37]Konstantinidis, K., Whelan, R.S., Kitsis, R.N., 2012. Mechanisms of cell death in heart disease. Arterioscler. Thromb. Vasc. Biol., 32(7):1552-1562.

[38]Lanza, I.R., Short, D.K., Short, K.R., et al., 2008. Endurance exercise as a countermeasure for aging. Diabetes, 57(11):2933-2942.

[39]Lerin, C., Rodgers, J.T., Kalume, D.E., et al., 2006. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1α. Cell Metab., 3(6):429-438.

[40]Li, H.L., Huang, Y., Zhang, C.N., et al., 2006. Epigallocathechin-3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and -independent signal pathways. Free Radic. Biol. Med., 40(10):1756-1775.

[41]Lindenmayer, G.E., Sordahl, L.A., Harigaya, S., et al., 1971. Some biochemical studies on subcellular systems isolated from fresh recipient human cardiac tissue obtained during transplantation. Am. J. Cardiol., 27(3):277-283.

[42]Lombard, D.B., Alt, F.W., Cheng, H.L., et al., 2007. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol., 27(24):8807-8814.

[43]Lorenzen, J.M., Martino, F., Thum, T., 2012. Epigenetic modifications in cardiovascular disease. Basic Res. Cardiol., 107(2):245.

[44]Lüscher, T.F., 2015. Risk factors for and management of heart failure. Eur. Heart J., 36(34):2267-2269.

[45]Marzetti, E., Csiszar, A., Dutta, D., et al., 2013. Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics. Am. J. Physiol. Heart Circ. Physiol., 305(4):H459-H476.

[46]Morita, H., Seidman, J., Seidman, C.E., 2005. Genetic causes of human heart failure. J. Clin. Invest., 115(3):518-526.

[47]Mozaffarian, D., Benjamin, E.J., Go, A.S., et al., 2016. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation, 133(4):e38-e360.

[48]Murphy, E., Steenbergen, C., 2008. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol. Rev., 88(2):581-609.

[49]Ohtani, T., Mohammed, S.F., Yamamoto, K., et al., 2012. Diastolic stiffness as assessed by diastolic wall strain is associated with adverse remodelling and poor outcomes in heart failure with preserved ejection fraction. Eur. Heart J., 33(14):1742-1749.

[50]Olivetti, G., Abbi, R., Quaini, F., et al., 1997. Apoptosis in the failing human heart. N. Engl. J. Med., 336(16):1131-1141.

[51]Onyango, P., Celic, I., McCaffery, J.M., et al., 2002. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. PNAS, 99(21):13653-13658.

[52]Pillai, V.B., Samant, S., Sundaresan, N.R., et al., 2015. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nat. Commun., 6:6656.

[53]Piper, H.M., Garcia-Dorado, D., Ovize, M., 1998. A fresh look at reperfusion injury. Cardiovasc. Res., 38(2):291-300.

[54]Richter, M., Kostin, S., 2015. The failing human heart is characterized by decreased numbers of telocytes as result of apoptosis and altered extracellular matrix composition. J. Cell. Mol. Med., 19(11):2597-2606.

[55]Rose, G., Dato, S., Altomare, K., et al., 2003. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp. Gerontol., 38(10):1065-1070.

[56]Schaper, J., Meiser, E., Stammler, G., 1985. Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts. Circ. Res., 56(3):377-391.

[57]Scher, M.B., Vaquero, A., Reinberg, D., 2007. SirT3 is a nuclear NAD⁺-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev., 21(8):920-928.

[58]Schwer, B., Verdin, E., 2008. Conserved metabolic regulatory functions of sirtuins. Cell Metab., 7(2):104-112.

[59]Smith, B.C., Settles, B., Hallows, W.C., et al., 2011. SIRT3 substrate specificity determined by peptide arrays and machine learning. ACS Chem. Biol., 6(2):146-157.

[60]Someya, S., Yu, W., Hallows, W.C., et al., 2010. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell, 143(5):802-812.

[61]Sordahl, L.A., McCollum, W.B., Wood, W.G., et al., 1973. Mitochondria and sarcoplasmic reticulum function in cardiac hypertrophy and failure. Am. J. Physiol., 224(3):497-502.

[62]Spann, J.F., Buccino, R.A., Sonnenblick, E.H., et al., 1967. Contractile state of cardiac muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circ. Res., 21(3):341-354.

[63]Stanley, W.C., Chandler, M.P., 2002. Energy metabolism in the normal and failing heart: potential for therapeutic interventions. Heart Fail. Rev., 7(2):115-130.

[64]Sundaresan, N.R., Samant, S.A., Pillai, V.B., et al., 2008. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol. Cell. Biol., 28(20):6384-6401.

[65]Sundaresan, N.R., Gupta, M., Kim, G., et al., 2009. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J. Clin. Invest., 119(9):2758-2771.

[66]Taegtmeyer, H., 1994. Energy metabolism of the heart: from basic concepts to clinical applications. Curr. Probl. Cardiol., 19(2):59-113.

[67]Tan, W.Q., Wang, K., Lv, D.Y., et al., 2008. Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase. J. Biol. Chem., 283(44):29730-29739.

[68]Towbin, J.A., 2014. Inherited cardiomyopathies. Circ. J., 78(10):2347-2356.

[69]Townsend, N., Nichols, M., Scarborough, P., et al., 2015. Cardiovascular disease in Europe—epidemiological update 2015. Eur. Heart J., 36(40):2696-2705.

[70]Tseng, A.H., Shieh, S.S., Wang, D.L., 2013. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic. Biol. Med., 63:222-234.

[71]van Empel, V.P., Bertrand, A.T., van Oort, R.J., et al., 2006. EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant. J. Am. Coll. Cardiol., 48(4):824-832.

[72]Velagaleti, R.S., Pencina, M.J., Murabito, J.M., et al., 2008. Long-term trends in the incidence of heart failure after myocardial infarction. Circulation, 118(20):2057-2062.

[73]Verdejo, H.E., del Campo, A., Troncoso, R., et al., 2012. Mitochondria, myocardial remodeling, and cardiovascular disease. Curr. Hypertens. Rep., 14(6):532-539.

[74]Wenzel, S., Rohde, C., Wingerning, S., et al., 2007. Lack of endothelial nitric oxide synthase-derived nitric oxide formation favors hypertrophy in adult ventricular cardiomyocytes. Hypertension, 49(1):193-200.

[75]Winnik, S., Auwerx, J., Sinclair, D.A., 2015. Protective effects of sirtuins in cardiovascular diseases: from bench to bedside. Eur. Heart J., 36(48):3404-3412.

[76]Xia, W., Geng, K., 2016. A sirtuin activator and an anti-inflammatory molecule-multifaceted roles of adjudin and its potential applications for aging-related diseases. Semin. Cell Dev. Biol., in press.

[77]Yancy, C.W., Jessup, M., Bozkurt, B., et al., 2013. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 128(16):1810-1852.

[78]Yang, X.J., Seto, E., 2007. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene, 26(37):5310-5318.

[79]Yue, Z., Ma, Y., You, J., et al., 2016. NMNAT3 is involved in the protective effect of SIRT3 in Ang II-induced cardiac hypertrophy. Exp. Cell Res., 347(2):261-273.

[80]Zeller, T., Blankenberg, S., Diemert, P., 2012. Genomewide association studies in cardiovascular disease—an update 2011. Clin. Chem., 58(1):92-103.

[81]Zeng, H., Vaka, V.R., He, X., et al., 2015. High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss. J. Cell. Mol. Med., 19(8):1847-1856.

[82]Zhang, L., Zhang, Z., Guo, H., et al., 2008. Na⁺/K⁺-ATPase-mediated signal transduction and Na⁺/K⁺-ATPase regulation. Fundam. Clin. Pharmacol., 22(6):615-621.

[83]Zhang, Y., Huo, Y., 2011. Early reperfusion strategy for acute myocardial infarction: a need for clinical implementation. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 12(8):629-632.

[84]Zou, X.J., Yang, L., Yao, S.L., 2008. Propofol depresses angiotensin II-induced cardiomyocyte hypertrophy in vitro. Exp. Biol. Med. (Maywood), 233(2):200-208.