Skip to main content
SpringerLink
Log in

Epigenetic and Nongenomic Roles for Histone Deacetylases in Heart Failure

  • Chapter
  • First Online:
Epigenetics in Cardiac Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 1))

  • 818 Accesses

Abstract

Heart failure due to systolic and/or diastolic ventricular dysfunction afflicts millions of people worldwide. Most heart failure drugs target signaling cascades that emanate from the cardiomyocyte cell surface. However, given the ability of numerous receptors to trigger adverse ventricular remodeling, it has been hypothesized that more efficacious therapeutic strategies would be based on inhibition of downstream “nodal” points that integrate upstream signals to convey a common pathway for heart failure pathogenesis. This chapter highlights data suggesting that a family of epigenetic regulatory enzymes, histone deacetylases (HDACs), represent such nodal points. We discuss recent findings that illustrate how HDACs not only control cardiac gene expression via epigenetic regulation, but also serve crucial non-genomic functions in the heart through deacetylation of non-histone proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Anand P, Brown JD, Lin CY, Qi J, Zhang R, Artero PC, Alaiti MA, Bullard J, Alazem K, Margulies KB, Cappola TP, Lemieux M, Plutzky J, Bradner JE, Haldar SM (2013) BET bromodomains mediate transcriptional pause release in heart failure. Cell 154:569–582

    CAS  PubMed  PubMed Central  Google Scholar 

  • Antos CL, McKinsey TA, Dreitz M, Hollingsworth LM, Zhang CL, Schreiber K, Rindt H, Gorczynski RJ, Olson EN (2003) Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors. J Biol Chem 278:28930–28937

    CAS  PubMed  Google Scholar 

  • Aune SE, Herr DJ, Mani SK, Menick DR (2014) Selective inhibition of class I but not class IIb histone deacetylases exerts cardiac protection from ischemia reperfusion. J Mol Cell Cardiol 72:138–145

    CAS  PubMed  PubMed Central  Google Scholar 

  • Backs J, Song K, Bezprozvannaya S, Chang S, Olson EN (2006) CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest 116:1853–1864

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blakeslee WW, Wysoczynski CL, Fritz KS, Nyborg JK, Churchill ME, McKinsey TA (2014) Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism. Cell Signal 26:2912–2920

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bradbury EM (1992) Reversible histone modifications and the chromosome cell cycle. Bioessays 14:9–16

    CAS  PubMed  Google Scholar 

  • Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R (2010) Chemical phylogenetics of histone deacetylases. Nat Chem Biol 6:238–243

    CAS  PubMed  PubMed Central  Google Scholar 

  • Braunwald E, Bristow MR (2000) Congestive heart failure: fifty years of progress. Circulation 102:IV14–IV23

    CAS  PubMed  Google Scholar 

  • Burchfield JS, Xie M, Hill JA (2013) Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 128:388–400

    PubMed  PubMed Central  Google Scholar 

  • Bush EW, McKinsey TA (2010) Protein acetylation in the cardiorenal axis: the promise of histone deacetylase inhibitors. Circ Res 106:272–284

    CAS  PubMed  Google Scholar 

  • Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP (2010) Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 132:10842–10846

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai R, Gu J, Sun H, Liu X, Mei W, Qi Y, Xue S, Ren S, Rabinowitz JE, Wang Y, Yeh ET, Cheng J (2015) Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy. J Mol Cell Cardiol 79:115–122

    CAS  PubMed  Google Scholar 

  • Cao DJ, Wang ZV, Battiprolu PK, Jiang N, Morales CR, Kong Y, Rothermel BA, Gillette TG, Hill JA (2011) Histone deacetylase (HDAC) inhibitors attenuate cardiac hypertrophy by suppressing autophagy. Proc Natl Acad Sci U S A 108:4123–4128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cardinale JP, Sriramula S, Pariaut R, Guggilam A, Mariappan N, Elks CM, Francis J (2010) HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. Hypertension 56:437–444

    CAS  PubMed  Google Scholar 

  • Cavasin MA, Demos-Davies K, Horn TR, Walker LA, Lemon DD, Birdsey N, Weiser-Evans MC, Harral J, Irwin DC, Anwar A, Yeager ME, Li M, Watson PA, Nemenoff RA, Buttrick PM, Stenmark KR, McKinsey TA (2012) Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism. Circ Res 110:739–748

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chakrabarti A, Oehme I, Witt O, Oliveira G, Sippl W, Romier C, Pierce RJ, Jung M (2015) HDAC8: a multifaceted target for therapeutic interventions. Trends Pharmacol Sci 36(7):481–92

    CAS  PubMed  Google Scholar 

  • Chang S, McKinsey TA, Zhang CL, Richardson JA, Hill JA, Olson EN (2004) Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol 24:8467–8476

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chang L, Kiriazis H, Gao XM, Du XJ, El-Osta A (2011) Cardiac genes show contextual SWI/SNF interactions with distinguishable gene activities. Epigenetics 6:760–768

    CAS  PubMed  Google Scholar 

  • Cho YK, Eom GH, Kee HJ, Kim HS, Choi WY, Nam KI, Ma JS, Kook H (2010) Sodium valproate, a histone deacetylase inhibitor, but not captopril, prevents right ventricular hypertrophy in rats. Circ J 74:760–770

    CAS  PubMed  Google Scholar 

  • Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840

    CAS  PubMed  Google Scholar 

  • Choudhary C, Weinert BT, Nishida Y, Verdin E, Mann M (2014) The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol 15:536–550

    CAS  PubMed  Google Scholar 

  • Cunliffe VT (2008) Eloquent silence: developmental functions of class I histone deacetylases. Curr Opin Genet Dev 18:404–410

    CAS  PubMed  PubMed Central  Google Scholar 

  • Davis FJ, Pillai JB, Gupta M, Gupta MP (2005) Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of alpha-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility. Am J Physiol Heart Circ Physiol 288:H1477–H1490

    CAS  PubMed  Google Scholar 

  • Demos-Davies KM, Ferguson BS, Cavasin MA, Mahaffey JH, Williams SM, Spiltoir JI, Schuetze KB, Horn TR, Chen B, Ferrara C, Scellini B, Piroddi N, Tesi C, Poggesi C, Jeong MY, McKinsey TA (2014) HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling. Am J Physiol Heart Circ Physiol 307:H252–H258

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eom GH, Nam YS, Oh JG, Choe N, Min HK, Yoo EK, Kang G, Nguyen VH, Min JJ, Kim JK, Lee IK, Bassel-Duby R, Olson EN, Park WJ, Kook H (2014) Regulation of acetylation of histone deacetylase 2 by p300/CBP-associated factor/histone deacetylase 5 in the development of cardiac hypertrophy. Circ Res 114:1133–1143

    CAS  PubMed  Google Scholar 

  • Fass DM, Shah R, Ghosh B, Hennig K, Norton S, Zhao WN, Reis SA, Klein PS, Mazitschek R, Maglathlin RL, Lewis TA, Haggarty SJ (2010) Effect of inhibiting histone deacetylase with short-chain carboxylic acids and their hydroxamic acid analogs on vertebrate development and neuronal chromatin. ACS Med Chem Lett 2:39–42

    PubMed  PubMed Central  Google Scholar 

  • Felsenfeld G, Groudine M (2003) Controlling the double helix. Nature 421:448–453

    PubMed  Google Scholar 

  • Ferguson BS, McKinsey TA (2015) Non-sirtuin histone deacetylases in the control of cardiac aging. J Mol Cell Cardiol 83:14–20

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ferguson BS, Harrison BC, Jeong MY, Reid BG, Wempe MF, Wagner FF, Holson EB, McKinsey TA (2013) Signal-dependent repression of DUSP5 by class I HDACs controls nuclear ERK activity and cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 110:9806–9811

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fleming CL, Ashton TD, Gaur V, McGee SL, Pfeffer FM (2014) Improved synthesis and structural reassignment of MC1568: a class IIa selective HDAC inhibitor. J Med Chem 57:1132–1135

    CAS  PubMed  Google Scholar 

  • Foster DB, Liu T, Rucker J, O’Meally RN, Devine LR, Cole RN, O’Rourke B (2013) The cardiac acetyl-lysine proteome. PLoS One 8, e67513

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gallo P, Latronico MV, Gallo P, Grimaldi S, Borgia F, Todaro M, Jones P, Gallinari P, De FR, Ciliberto G, Steinkuhler C, Esposito G, Condorelli G (2008) Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure. Cardiovasc Res 80:416–424

    CAS  PubMed  Google Scholar 

  • Gao L, Cueto MA, Asselbergs F, Atadja P (2002) Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 277:25748–25755

    CAS  PubMed  Google Scholar 

  • Gregoretti IV, Lee YM, Goodson HV (2004) Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 338:17–31

    CAS  PubMed  Google Scholar 

  • Haldar SM, McKinsey TA (2014) BET-ting on chromatin-based therapeutics for heart failure. J Mol Cell Cardiol 74:98–102

    CAS  PubMed  Google Scholar 

  • Harrison BC, Roberts CR, Hood DB, Sweeney M, Gould JM, Bush EW, McKinsey TA (2004) The CRM1 nuclear export receptor controls pathological cardiac gene expression. Mol Cell Biol 24:10636–10649

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes JR, Roberts N, McGowan S, Hay D, Giannoulatou E, Lynch M, De Gobbi GM, Taylor S, Gibbons R, Higgs DR (2014) Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment. Nat Genet 46:205–212

    CAS  PubMed  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    CAS  PubMed  Google Scholar 

  • Jones P, Altamura S, De Francesco R, Gallinari P, Lahm A, Neddermann P, Rowley M, Serafini S, Steinkuhler C (2008) Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases. Bioorg Med Chem Lett 18:1814–1819

    CAS  PubMed  Google Scholar 

  • Kang SH, Seok YM, Song MJ, Lee HA, Kurz T, Kim I (2015) Histone deacetylase inhibition attenuates cardiac hypertrophy and fibrosis through acetylation of mineralocorticoid receptor in spontaneously hypertensive rats. Mol Pharmacol 87:782–791

    CAS  PubMed  Google Scholar 

  • Kee HJ, Sohn IS, Nam KI, Park JE, Qian YR, Yin Z, Ahn Y, Jeong MH, Bang YJ, Kim N, Kim JK, Kim KK, Epstein JA, Kook H (2006) Inhibition of histone deacetylation blocks cardiac hypertrophy induced by angiotensin II infusion and aortic banding. Circulation 113:51–59

    CAS  PubMed  Google Scholar 

  • Kee HJ, Eom GH, Joung H, Shin S, Kim JR, Cho YK, Choe N, Sim BW, Jo D, Jeong MH, Kim KK, Seo JS, Kook H (2008) Activation of histone deacetylase 2 by inducible heat shock protein 70 in cardiac hypertrophy. Circ Res 103:1259–1269

    CAS  PubMed  Google Scholar 

  • Kee HJ, Bae EH, Park S, Lee KE, Suh SH, Kim SW, Jeong MH (2013) HDAC inhibition suppresses cardiac hypertrophy and fibrosis in DOCA-salt hypertensive rats via regulation of HDAC6/HDAC8 enzyme activity. Kidney Blood Press Res 37:229–239

    CAS  PubMed  Google Scholar 

  • Kelly RD, Cowley SM (2013) The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts. Biochem Soc Trans 41:741–749

    CAS  PubMed  Google Scholar 

  • Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, Park WJ, Hajjar RJ (2011) SUMO1-dependent modulation of SERCA2a in heart failure. Nature 477:601–605

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim EY, Chen L, Ma Y, Yu W, Chang J, Moskowitz IP, Wang J (2012) Enhanced desumoylation in murine hearts by overexpressed SENP2 leads to congenital heart defects and cardiac dysfunction. J Mol Cell Cardiol 52:638–649

    CAS  PubMed  Google Scholar 

  • Lahm A, Paolini C, Pallaoro M, Nardi MC, Jones P, Neddermann P, Sambucini S, Bottomley MJ, Lo SP, Carfi A, Koch U, De FR, Steinkuhler C, Gallinari P (2007) Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc Natl Acad Sci U S A 104:17335–17340

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lemon DD, Horn TR, Cavasin MA, Jeong MY, Haubold KW, Long CS, Irwin DC, McCune SA, Chung E, Leinwand LA, McKinsey TA (2011) Cardiac HDAC6 catalytic activity is induced in response to chronic hypertension. J Mol Cell Cardiol 51:41–50

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lemon DD, Harrison BC, Horn TR, Stratton MS, Ferguson BS, Wempe MF, McKinsey TA (2015) Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle. FEBS Lett 589:1080–1088

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Chen S, Cleary RA, Wang R, Gannon OJ, Seto E, Tang DD (2014) Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues. Am J Physiol Cell Physiol 307:C288–C295

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Peng L, Seto E, Huang S, Qiu Y (2012) Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. J Biol Chem 287:29168–29174

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lobera M, Madauss KP, Pohlhaus DT, Wright QG, Trocha M, Schmidt DR, Baloglu E, Trump RP, Head MS, Hofmann GA, Murray-Thompson M, Schwartz B, Chakravorty S, Wu Z, Mander PK, Kruidenier L, Reid RA, Burkhart W, Turunen BJ, Rong JX, Wagner C, Moyer MB, Wells C, Hong X, Moore JT, Williams JD, Soler D, Ghosh S, Nolan MA (2013) Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol 9:319–325

    CAS  PubMed  Google Scholar 

  • Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV (2012) Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns. Cell Rep 2:419–431

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mai A, Massa S, Pezzi R, Simeoni S, Rotili D, Nebbioso A, Scognamiglio A, Altucci L, Loidl P, Brosch G (2005) Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. J Med Chem 48:3344–3353

    CAS  PubMed  Google Scholar 

  • Mani SK, Kern CB, Kimbrough D, Addy B, Kasiganesan H, Rivers WT, Patel RK, Chou JC, Spinale FG, Mukherjee R, Menick DR (2015) Inhibition of class I histone deacetylase activity represses matrix metalloproteinase-2 and -9 expression and preserves LV function postmyocardial infarction. Am J Physiol Heart Circ Physiol 308:H1391–H1401

    PubMed  PubMed Central  Google Scholar 

  • Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S, Horinouchi S, Yoshida M (2002) In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J 21:6820–6831

    CAS  PubMed  PubMed Central  Google Scholar 

  • McKinsey TA (2007) Derepression of pathological cardiac genes by members of the CaM kinase superfamily. Cardiovasc Res 73:667–677

    CAS  PubMed  Google Scholar 

  • McKinsey TA (2012) Therapeutic potential for HDAC inhibitors in the heart. Annu Rev Pharmacol Toxicol 52:303–319

    CAS  PubMed  Google Scholar 

  • McKinsey TA, Olson EN (2004) Dual roles of histone deacetylases in the control of cardiac growth. Novartis Found Symp 259:132–141

    CAS  PubMed  Google Scholar 

  • McLendon PM, Ferguson BS, Osinska H, Bhuiyan MS, James J, McKinsey TA, Robbins J (2014) Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy. Proc Natl Acad Sci U S A 111:E5178–E5186

    CAS  PubMed  PubMed Central  Google Scholar 

  • McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993–1004

    PubMed  Google Scholar 

  • Meredith EL, Beattie K, Burgis R, Capparelli M, Chapo J, Dipietro L, Gamber G, Enyedy I, Hood DB, Hosagrahara V, Jewell C, Koch KA, Lee W, Lemon DD, McKinsey TA, Miranda K, Pagratis N, Phan D, Plato C, Rao C, Rozhitskaya O, Soldermann N, Springer C, van Eis M, Vega RB, Yan W, Zhu Q, Monovich LG (2010a) Identification of potent and selective amidobipyridyl inhibitors of protein kinase D. J Med Chem 53:5422–5438

    CAS  PubMed  Google Scholar 

  • Meredith EL, Ardayfio O, Beattie K, Dobler MR, Enyedy I, Gaul C, Hosagrahara V, Jewell C, Koch K, Lee W, Lehmann H, McKinsey TA, Miranda K, Pagratis N, Pancost M, Patnaik A, Phan D, Plato C, Qian M, Rajaraman V, Rao C, Rozhitskaya O, Ruppen T, Shi J, Siska SJ, Springer C, van Eis M, Vega RB, von Matt A, Yang L, Yoon T, Zhang JH, Zhu N, Monovich LG (2010b) Identification of orally available naphthyridine protein kinase D inhibitors. J Med Chem 53:5400–5421

    CAS  PubMed  Google Scholar 

  • Monovich L, Vega RB, Meredith E, Miranda K, Rao C, Capparelli M, Lemon DD, Phan D, Koch KA, Chapo JA, Hood DB, McKinsey TA (2010) A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase. FEBS Lett 584:631–637

    CAS  PubMed  Google Scholar 

  • Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J, Qi X, Hill JA, Richardson JA, Olson EN (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 21:1790–1802

    CAS  PubMed  PubMed Central  Google Scholar 

  • Montgomery RL, Potthoff MJ, Haberland M, Qi X, Matsuzaki S, Humphries KM, Richardson JA, Bassel-Duby R, Olson EN (2008) Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. J Clin Invest 118:3588–3597

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER III, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB (2015) Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 131:e29–e322

    PubMed  Google Scholar 

  • Newman JC, He W, Verdin E (2012) Mitochondrial protein acylation and intermediary metabolism: regulation by sirtuins and implications for metabolic disease. J Biol Chem 287:42436–42443

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nural-Guvener HF, Zakharova L, Nimlos J, Popovic S, Mastroeni D, Gaballa MA (2014) HDAC class I inhibitor, Mocetinostat, reverses cardiac fibrosis in heart failure and diminishes CD90+ cardiac myofibroblast activation. Fibrogenesis Tissue Repair 7:10

    PubMed  PubMed Central  Google Scholar 

  • Oehme I, Lodrini M, Brady NR, Witt O (2013a) Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas. Autophagy 9:2163–2165

    CAS  PubMed  Google Scholar 

  • Oehme I, Linke JP, Bock BC, Milde T, Lodrini M, Hartenstein B, Wiegand I, Eckert C, Roth W, Kool M, Kaden S, Grone HJ, Schulte JH, Lindner S, Hamacher-Brady A, Brady NR, Deubzer HE, Witt O (2013b) Histone deacetylase 10 promotes autophagy-mediated cell survival. Proc Natl Acad Sci U S A 110:E2592–E2601

    CAS  PubMed  PubMed Central  Google Scholar 

  • Olson DE, Sleiman SF, Bourassa MW, Wagner FF, Gale JP, Zhang YL, Ratan RR, Holson EB (2015) Hydroxamate-based histone deacetylase inhibitors can protect neurons from oxidative stress via a histone deacetylase-independent catalase-like mechanism. Chem Biol 22:439–445

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ooi JY, Tuano NK, Rafehi H, Gao XM, Ziemann M, Du XJ, El-Osta A (2015) HDAC inhibition attenuates cardiac hypertrophy by acetylation and deacetylation of target genes. Epigenetics 10:418–430

    PubMed  PubMed Central  Google Scholar 

  • Papait R, Cattaneo P, Kunderfranco P, Greco C, Carullo P, Guffanti A, Vigano V, Stirparo GG, Latronico MV, Hasenfuss G, Chen J, Condorelli G (2013) Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy. Proc Natl Acad Sci U S A 110:20164–20169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Samant SA, Pillai VB, Sundaresan NR, Shroff SG, Gupta MP (2015) Histone Deacetylase 3 (HDAC3)-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity. J Biol Chem 290:15559–15569

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sayed D, He M, Yang Z, Lin L, Abdellatif M (2013) Transcriptional regulation patterns revealed by high resolution chromatin immunoprecipitation during cardiac hypertrophy. J Biol Chem 288:2546–2558

    CAS  PubMed  Google Scholar 

  • Scholz C, Weinert BT, Wagner SA, Beli P, Miyake Y, Qi J, Jensen LJ, Streicher W, McCarthy AR, Westwood NJ, Lain S, Cox J, Matthias P, Mann M, Bradner JE, Choudhary C (2015) Acetylation site specificities of lysine deacetylase inhibitors in human cells. Nat Biotechnol 33:415–423

    CAS  PubMed  Google Scholar 

  • Schubeler D, MacAlpine DM, Scalzo D, Wirbelauer C, Kooperberg C, van Leeuwen F, Gottschling DE, O’Neill LP, Turner BM, Delrow J, Bell SP, Groudine M (2004) The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev 18:1263–1271

    PubMed  PubMed Central  Google Scholar 

  • Shahbazian MD, Grunstein M (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76:75–100

    CAS  PubMed  Google Scholar 

  • Sharifi-Sanjani M, Shoushtari AH, Quiroz M, Baust J, Sestito SF, Mosher M, Ross M, McTiernan CF, St Croix CM, Bilonick RA, Champion HC, Isenberg JS (2014) Cardiac CD47 drives left ventricular heart failure through Ca2+−CaMKII-regulated induction of HDAC3. J Am Heart Assoc 3:e000670

    PubMed  PubMed Central  Google Scholar 

  • Shiio Y, Eisenman RN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A 100:13225–13230

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spiltoir JI, Stratton MS, Cavasin MA, Demos-Davies K, Reid BG, Qi J, Bradner JE, McKinsey TA (2013) BET acetyl-lysine binding proteins control pathological cardiac hypertrophy. J Mol Cell Cardiol 63:175–179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Z, Singh N, Mullican SE, Everett LJ, Li L, Yuan L, Liu X, Epstein JA, Lazar MA (2011) Diet-induced lethality due to deletion of the Hdac3 gene in heart and skeletal muscle. J Biol Chem 286:33301–33309

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Z, Feng D, Fang B, Mullican SE, You SH, Lim HW, Everett LJ, Nabel CS, Li Y, Selvakumaran V, Won KJ, Lazar MA (2013) Deacetylase-independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor. Mol Cell 52:769–782

    CAS  PubMed  Google Scholar 

  • Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, Zhao Y (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146:1016–1028

    CAS  PubMed  PubMed Central  Google Scholar 

  • Terbach N, Williams RS (2009) Structure-function studies for the panacea, valproic acid. Biochem Soc Trans 37:1126–1132

    CAS  PubMed  Google Scholar 

  • Tilemann L, Lee A, Ishikawa K, Aguero J, Rapti K, Santos-Gallego C, Kohlbrenner E, Fish KM, Kho C, & Hajjar RJ (2013) SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure. Sci Transl Med 5: 211ra159.

    Google Scholar 

  • Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F (2008) HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 18:291–297

    CAS  PubMed  Google Scholar 

  • Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (2004) Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5. Mol Cell Biol 24:8374–8385

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wagner FF, Weiwer M, Lewis MC, Holson EB (2013) Small molecule inhibitors of zinc-dependent histone deacetylases. Neurotherapeutics 10:589–604

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Osinska H, Klevitsky R, Gerdes AM, Nieman M, Lorenz J, Hewett T, Robbins J (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res 89:84–91

    CAS  PubMed  Google Scholar 

  • Wang Y, Fischle W, Cheung W, Jacobs S, Khorasanizadeh S, Allis CD (2004) Beyond the double helix: writing and reading the histone code. Novartis Found Symp 259:3–17

    CAS  PubMed  Google Scholar 

  • Wang S, Sun H, Ma J, Zang C, Wang C, Wang J, Tang Q, Meyer CA, Zhang Y, Liu XS (2013) Target analysis by integration of transcriptome and ChIP-seq data with BETA. Nat Protoc 8:2502–2515

    CAS  PubMed  PubMed Central  Google Scholar 

  • West AC, Johnstone RW (2014) New and emerging HDAC inhibitors for cancer treatment. J Clin Invest 124:30–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Williams SM, Golden-Mason L, Ferguson BS, Schuetze KB, Cavasin MA, Demos-Davies K, Yeager ME, Stenmark KR, McKinsey TA (2014) Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts and circulating fibrocytes. J Mol Cell Cardiol 67:112–125

    CAS  PubMed  Google Scholar 

  • Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguere V (2010) An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha. Mol Endocrinol 24:1349–1358

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xie Z, Dai J, Dai L, Tan M, Cheng Z, Wu Y, Boeke JD, Zhao Y (2012) Lysine succinylation and lysine malonylation in histones. Mol Cell Proteomics 11:100–107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xie M, Burchfield JS, Hill JA (2013) Pathological ventricular remodeling: therapies: part 2 of 2. Circulation 128:1021–1030

    PubMed  Google Scholar 

  • Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31:449–461

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang CL, McKinsey TA, Chang S, Antos CL, Hill JA, Olson EN (2002) Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy. Cell 110:479–488

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang D, Wu CT, Qi X, Meijering RA, Hoogstra-Berends F, Tadevosyan A, Cubukcuoglu DG, Durdu S, Akar AR, Sibon OC, Nattel S, Henning RH, Brundel BJ (2014) Activation of histone deacetylase-6 induces contractile dysfunction through derailment of alpha-tubulin proteostasis in experimental and human atrial fibrillation. Circulation 129:346–358

    CAS  PubMed  Google Scholar 

  • Zhao L, Chen CN, Hajji N, Oliver E, Cotroneo E, Wharton J, Wang D, Li M, McKinsey TA, Stenmark KR, Wilkins MR (2012) Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. Circulation 126:455–467

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Molly K. McKinsey for assistance with graphics. W.W.B. was funded by the University of Colorado Denver Pharmacology Program NIH T32 Training Grant (GM007635), and T.A.M. was supported by grants from the NIH (R01HL116848, R21AG043822, R01HL127240) and American Heart Association (13GRNT14510001).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA

    Weston W. Blakeslee & Timothy A. McKinsey

  2. Medical Scientist Training Program, University of Colorado Denver, Aurora, CO, USA

    Philip D. Tatman & Timothy A. McKinsey

  3. Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA

    Philip D. Tatman & Timothy A. McKinsey

  4. Consortium for Fibrosis Research and Translation, University of Colorado Denver, Aurora, CO, USA

    Timothy A. McKinsey

Authors
  1. Weston W. Blakeslee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip D. Tatman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Timothy A. McKinsey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy A. McKinsey .

Editor information

Editors and Affiliations

  1. Department of Molecular, Cardiology and Epigenetics, University of Heidelberg, Heidelberg, Germany

    Johannes Backs

  2. Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA

    Timothy A. McKinsey

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Blakeslee, W.W., Tatman, P.D., McKinsey, T.A. (2016). Epigenetic and Nongenomic Roles for Histone Deacetylases in Heart Failure. In: Backs, J., McKinsey, T.A. (eds) Epigenetics in Cardiac Disease. Cardiac and Vascular Biology, vol 1. Springer, Cham. https://doi.org/10.1007/978-3-319-41457-7_9

Download citation

Publish with us

Policies and ethics

Search

Navigation