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Gene Profiling of the Failing Heart: Epigenetics

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Heart Failure

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

In spite of continuing intensive basic and clinical research and new diagnostic modalities and treatment of cardiovascular diseases are becoming available, heart failure (HF) remains a severe health problem of dramatic proportions. Nevertheless, in the current era of post-genomics medicine, the development of novel molecular and cellular technologies have awaken a sense of optimism that we will finally be able to unravel the mechanisms of a number of multigenic diseases, in particular, the complex spider-web like HF. These exciting technologies are paving the way to simultaneously assess the expression of tens of thousands of gene transcripts in a single experiment, providing a resolution and precision of phenotypic characterization not previously possible. Within the heart, many examples of genetic and protein changes correlated with functional alterations have been noted both during normal development and during the development of HF from a variety of causes.

In this chapter, the molecular basis of HF with focus on gene function and expression, epigenetics, and metabolic and calcium cycling will be discussed.

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References

  1. Mann DL (1999) Mechanisms and models in heart failure: a combinatorial approach. Circulation 100:999–1008

    Article  PubMed  CAS  Google Scholar 

  2. Kittleson MM, Hare JM (2005) Molecular signature analysis: using the myocardial transcriptome as a biomarker in cardiovascular disease. Trends Cardiovasc Med 15:130–138

    Article  PubMed  CAS  Google Scholar 

  3. Sanoudou D, Vafiadaki E, Arvanitis DA, Kranias E, Kontrogianni-Konstantopoulos A (2005) Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies. Physiol Genomics 21:131–143

    Article  PubMed  CAS  Google Scholar 

  4. Tan FL, Moravec CS, Li J, Apperson-Hansen C, McCarthy PM, Young JB, Bond M (2002) The gene expression fingerprint of human heart failure. Proc Natl Acad Sci USA 99:11387–11392

    Article  PubMed  CAS  Google Scholar 

  5. Steenman M, Lamirault G, Le Meur N, Le Cunff M, Escande D, Leger JJ (2005) Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays. Eur J Heart Fail 7:157–165

    Article  PubMed  CAS  Google Scholar 

  6. Renlund DG, Taylor DO, Kfoury AG, Shaddy RS (1999) rules: historical background and implications for transplantation management. United Network for Organ Sharing. J Heart Lung Transplant 18:1065–1070

    Article  PubMed  CAS  Google Scholar 

  7. Kaab S, Barth AS, Margerie D et al (2004) Global gene expression in human myocardium-oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure. J Mol Med 82:308–316

    Article  PubMed  CAS  Google Scholar 

  8. Hwang JJ, Allen PD, Tseng GC, Lam CW, Fananapazir L, Dzau VJ, Liew CC (2002) Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics 10:31–44

    PubMed  CAS  Google Scholar 

  9. Hall JL, Grindle S, Han X et al (2004) Genomic profiling of the human heart before and after mechanical support with a ventricular assist device reveals alterations in vascular signaling networks. Physiol Genomics 17:283–291

    Article  PubMed  CAS  Google Scholar 

  10. Kittleson MM, Minhas KM, Irizarry RA et al (2005) Gene expression in giant cell myocarditis: altered expression of immune response genes. Int J Cardiol 102:333–340

    Article  PubMed  Google Scholar 

  11. Carey VJ, Gentry J, Whalen E, Gentleman R (2005) Network structures and algorithms in Bioconductor. Bioinformatics 21:135–136

    Article  PubMed  CAS  Google Scholar 

  12. Simon R, Radmacher MD, Dobbin K, McShane LM (2003) Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification. J Natl Cancer Inst 95:14–18

    Article  PubMed  CAS  Google Scholar 

  13. Kittleson MM, Ye SQ, Irizarry RA et al (2004) Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 110:3444–3451

    Article  PubMed  CAS  Google Scholar 

  14. Heidecker B, Kasper EK, Wittstein IS et al (2008) Transcriptomic biomarkers for individual risk assessment in new-onset heart failure. Circulation 118:238–246

    Article  PubMed  CAS  Google Scholar 

  15. Song Q, Schmidt AG, Hahn HS et al (2003) Rescue of cardiomyocyte dysfunction by phospholamban ablation does not prevent ventricular failure in genetic hypertrophy. J Clin Invest 111:859–867

    PubMed  CAS  Google Scholar 

  16. Wilkie GS, Dickson KS, Gray NK (2003) Regulation of mRNA translation by 5′- and 3′-UTR-binding factors. Trends Biochem Sci 28:182–188

    Article  PubMed  CAS  Google Scholar 

  17. Schott P, Singer SS, Kogler H et al (2005) Pressure overload and neurohumoral activation differentially affect the myocardial proteome. Proteomics 5:1372–1381

    Article  PubMed  CAS  Google Scholar 

  18. Figueredo VM, Camacho SA (1995) Basic mechanisms of myocardial dysfunction: cellular pathophysiology of heart failure. Curr Opin Cardiol 10:246–252

    Article  PubMed  CAS  Google Scholar 

  19. Barany M (1967) ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol 50:197–218

    Article  PubMed  Google Scholar 

  20. Morano M, Zacharzowski U, Maier M, Lange PE, Alexi-Meskishvili V, Haase H, Morano I (1996) Regulation of human heart contractility by essential myosin light chain isoforms. J Clin Invest 98:467–473

    Article  PubMed  CAS  Google Scholar 

  21. Braz JC, Bueno OF, Liang Q et al (2003) Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J Clin Invest 111:1475–1486

    PubMed  CAS  Google Scholar 

  22. Dorn GW, Molkentin JD (2004) Manipulating cardiac contractility in heart failure: data from mice and men. Circulation 109:150–158

    Article  PubMed  Google Scholar 

  23. Boluyt MO, O’Neill L, Meredith AL et al (1994) Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res 75:23–32

    Article  PubMed  CAS  Google Scholar 

  24. Yung CK, Halperin VL, Tomaselli GF, Winslow RL (2004) Gene expression profiles in end-stage human idiopathic dilated cardiomyopathy: altered expression of apoptotic and cytoskeletal genes. Genomics 83:281–297

    Article  PubMed  CAS  Google Scholar 

  25. Komajda M, Charron P (2004) A new approach for the identification of modifier genes in heart failure. Pharmacogenomics J 4:221–223

    Article  PubMed  CAS  Google Scholar 

  26. Le Corvoisier P, Park HY, Carlson KM, Marchuk DA, Rockman HA (2003) Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy. Hum Mol Genet 12:3097–3107

    Article  PubMed  CAS  Google Scholar 

  27. Gupta S, Young D, Maitra RK et al (2008) Prevention of cardiac hypertrophy and heart failure by silencing of NF-kappaB. J Mol Biol 375:637–649

    Article  PubMed  CAS  Google Scholar 

  28. Frantz S, Fraccarollo D, Wagner H et al (2003) Sustained activation of nuclear factor kappa B and activator protein 1 in chronic heart failure. Cardiovasc Res 57:749–756

    Article  PubMed  CAS  Google Scholar 

  29. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114

    Article  PubMed  CAS  Google Scholar 

  30. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  PubMed  CAS  Google Scholar 

  31. Borchert GM, Lanier W, Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13:1097–1101

    Article  PubMed  CAS  Google Scholar 

  32. Wang Z, Luo X, Lu Y, Yang B (2008) miRNAs at the heart of the matter. J Mol Med 86:771–783

    Article  PubMed  CAS  Google Scholar 

  33. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97–100

    Article  PubMed  CAS  Google Scholar 

  34. Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21:1469–1477

    Article  PubMed  Google Scholar 

  35. Obernosterer G, Leuschner PJ, Alenius M, Martinez J (2006) Post-transcriptional regulation of microRNA expression. RNA 12:1161–1167

    Article  PubMed  CAS  Google Scholar 

  36. Mineno J, Okamoto S, Ando T et al (2006) The expression profile of microRNAs in mouse embryos. Nucleic Acids Res 34:1765–1771

    Article  PubMed  CAS  Google Scholar 

  37. Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM (2006) Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev 20:2202–2207

    Article  PubMed  CAS  Google Scholar 

  38. Wulczyn FG, Smirnova L, Rybak A et al (2007) Post-transcriptional regulation of the let-7 microRNA during neural cell specification. FASEB J 21:415–426

    Article  PubMed  CAS  Google Scholar 

  39. Suh MR, Lee Y, Kim JY et al (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498

    Article  PubMed  CAS  Google Scholar 

  40. Karp X, Ambros V (2005) Developmental biology. Encountering microRNAs in cell fate signaling. Science 310:1288–1289

    Article  PubMed  CAS  Google Scholar 

  41. Thomas JR, Hergenrother PJ (2008) Targeting RNA with small molecules. Chem Rev 108:1171–1224

    Article  PubMed  CAS  Google Scholar 

  42. Rajewsky N, Socci ND (2004) Computational identification of microRNA targets. Dev Biol 267:529–535

    Article  PubMed  CAS  Google Scholar 

  43. Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297

    Article  PubMed  CAS  Google Scholar 

  44. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  PubMed  CAS  Google Scholar 

  45. Xu P, Guo M, Hay BA (2004) MicroRNAs and the regulation of cell death. Trends Genet 20:617–624

    Article  PubMed  CAS  Google Scholar 

  46. Thum T, Galuppo P, Wolf C et al (2007) MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 116:258–267

    Article  PubMed  CAS  Google Scholar 

  47. O’Rourke JR, Georges SA, Seay HR et al (2007) Essential role for Dicer during skeletal muscle development. Dev Biol 311:359

    Article  PubMed  CAS  Google Scholar 

  48. Chen JF, Murchison EP, Tang R et al (2008) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci USA 105:2111–2116

    Article  PubMed  CAS  Google Scholar 

  49. Wang Z, Wang DZ, Hockemeyer D, McAnally J, Nordheim A, Olson EN (2004) Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression. Nature 428:185–189

    Article  PubMed  CAS  Google Scholar 

  50. Wang DZ, Olson EN (2004) Control of smooth muscle development by the. myocardin family of transcriptional coactivators. Curr Opin Genet Dev 14:558–566

    Article  PubMed  CAS  Google Scholar 

  51. Chen JF, Mandel EM, Thomson JM et al (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233

    Article  PubMed  CAS  Google Scholar 

  52. Liu N, Williams AH, Kim Y et al (2007) An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proc Natl Acad Sci USA 104:20844–20849

    Article  PubMed  CAS  Google Scholar 

  53. van Rooij E, Liu N, Olson EN (2008) MicroRNAs flex their muscles. Trends Genet 24:159–166

    Article  PubMed  CAS  Google Scholar 

  54. Xu C, Lu Y, Pan Z et al (2007) The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci 120:3045–3052

    Article  PubMed  CAS  Google Scholar 

  55. Yang B, Lin H, Xiao J et al (2007) The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 13:486–491

    Article  PubMed  CAS  Google Scholar 

  56. Scalbert E, Bril A (2008) Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol 8:181–188

    Article  PubMed  CAS  Google Scholar 

  57. Callis TE, Wang DZ (2008) Taking microRNAs to heart. Trends Mol Med 14:254–260

    Article  PubMed  CAS  Google Scholar 

  58. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  PubMed  CAS  Google Scholar 

  59. Krek A, Grün D, Poy MN et al (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  PubMed  CAS  Google Scholar 

  60. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158

    PubMed  CAS  Google Scholar 

  61. van Rooij E, Sutherland LB, Liu N et al (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hyper-trophy and heart failure. Proc Natl Acad Sci USA 103:18255–18260

    Article  PubMed  CAS  Google Scholar 

  62. Carè A, Catalucci D, Felicetti F et al (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13:613–618

    Article  PubMed  CAS  Google Scholar 

  63. Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100:416–424

    Article  PubMed  CAS  Google Scholar 

  64. Liu L, Li Y, Tollefsbol TO (2008) Gene-environment interactions and epigenetic basis of human diseases. Curr Issues Mol Biol 10:25–36

    PubMed  CAS  Google Scholar 

  65. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN (2007) Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316:575–579

    Article  PubMed  CAS  Google Scholar 

  66. Cheng Y, Ji R, Yue J et al (2007) MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol 170:1831–1840

    Article  PubMed  CAS  Google Scholar 

  67. Tatsuguchi M, Seok HY, Callis TE et al (2007) Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J Mol Cell Cardiol 42:1137–1141

    Article  PubMed  CAS  Google Scholar 

  68. McCarthy JJ, Esser KA (2007) MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J Appl Physiol 102:306–313

    Article  PubMed  CAS  Google Scholar 

  69. Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436:214–220

    Article  PubMed  CAS  Google Scholar 

  70. Zhao Y, Ransom JF, Li A et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell 129:303–317

    Article  PubMed  CAS  Google Scholar 

  71. Kwon C, Han Z, Olson EN, Srivastava D (2005) MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci USA 102:18986–18991

    Article  PubMed  CAS  Google Scholar 

  72. Xiao J, Luo X, Lin H et al (2007) MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J Biol Chem 282:12363–12367

    Article  PubMed  CAS  Google Scholar 

  73. Anderson C, Catoe H, Werner R (2006) MIR-206 regulates connexin 43 expression during skeletal muscle development. Nucleic Acids Res 34:5863–5871

    Article  PubMed  CAS  Google Scholar 

  74. Rosenberg MI, Georges SA, Asawachaicharn A, Analau E, Tapscott SJ (2006) MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. J Cell Biol 175:77–85

    Article  PubMed  CAS  Google Scholar 

  75. Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A (2006) Muscle specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174:677–687

    Article  PubMed  CAS  Google Scholar 

  76. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336

    Article  PubMed  CAS  Google Scholar 

  77. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647

    Article  PubMed  CAS  Google Scholar 

  78. Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301:798–802

    Article  PubMed  CAS  Google Scholar 

  79. Reinhart BJ, Bartel DP (2002) Small RNAs correspond to centromeric heterochrtomatin repeats. Science 297:1831

    Article  PubMed  CAS  Google Scholar 

  80. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA (2002) Regulation of heterochromatin silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837

    Article  PubMed  CAS  Google Scholar 

  81. Mette MF, Aufsatz W, van der Winder J, Matzke MA, Matzke AJM (2000) Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J 19:5194–5201

    Article  PubMed  CAS  Google Scholar 

  82. Metzger JM (2002) HDAC lightens a heavy heart. Nat Med 8:1078–1079

    Article  PubMed  CAS  Google Scholar 

  83. Gusterson RJ, Jazrawi E, Adcock IM, Latchman DS (2003) The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity. J Biol Chem 278:6838–6847

    Article  PubMed  CAS  Google Scholar 

  84. 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

    Article  PubMed  CAS  Google Scholar 

  85. Hamamori Y, Schneider MD (2003) HATs off to Hop: recruitment of a class I histone deacetylase incriminates a novel transcriptional pathway that opposes cardiac hypertrophy. J Clin Invest 112:824–826

    PubMed  CAS  Google Scholar 

  86. Kook H, Lepore JJ, Gitler AD et al (2003) Cardiac hypertrophy and histone deacetylase-dependent transcriptional repression mediated by the atypical homeodomain protein Hop. J Clin Invest 112:863–871

    PubMed  CAS  Google Scholar 

  87. Kim YO, Park SJ, Balaban RS, Nirenberg M, Kim Y (2004) A functional genomic screen for cardiogenic genes using RNA interference in developing Drosophila embryos. Proc Natl Acad Sci USA 101:159–164

    Article  PubMed  CAS  Google Scholar 

  88. Novik KL, Nimmrich I, Genc B, Maier S, Piepenbrock C, Olek A, Beck S (2002) Epigenomics: genome-wide study of methylation phenomena. Curr Issues Mol Biol 4:111–289

    PubMed  CAS  Google Scholar 

  89. Bird AP (1986) CpG rich islands and the function of DNA methylation. Nature 321:209–213

    Article  PubMed  CAS  Google Scholar 

  90. Beggs AH, Migeon BR (1989) Chromatin loop structure of the human X chromosome: relevance to X inactivation and CpG clusters. Mol Cell Biol 9:2322–2331

    PubMed  CAS  Google Scholar 

  91. Ferguson-Smith AC, Sasaki H, Cattanach BM, Surani MA (1993) Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature 362:751–755

    Article  PubMed  CAS  Google Scholar 

  92. D’Cruz LG, Baboonian C, Phillimore HE et al (2000) Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic cardiomyopathy. J Med Genet 37:E18

    Article  PubMed  Google Scholar 

  93. Smilinich NJ, Day CD, Fitzpatrick GV et al (1999) A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proc Natl Acad Sci USA 196:8064–8069

    Article  Google Scholar 

  94. Cerrato F, Vernucci M, Pedone PV et al (2002) The 5′ end of the KCNQ1OT1 gene is hypomethylated in the Beckwith-Wiedemann syndrome. Hum Genet 111:105–107

    Article  PubMed  Google Scholar 

  95. Choi YS, Kim S, Pak YK (2001) Mitochondrial transcription factor A (mtTFA) and diabetes. Diabetes Res Clin Pract 54:S3–S9

    Article  PubMed  CAS  Google Scholar 

  96. Post WS, Goldschmidt-Clermont PJ, Wilhide CC et al (1999) Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc Res 43:985–991

    Article  PubMed  CAS  Google Scholar 

  97. Chen P, Poddar R, Tipa EV, Jacobsen DW (1999) Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease. Adv Enzyme Regul 39:93–109

    Article  PubMed  CAS  Google Scholar 

  98. James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA (2002) Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 132:2361S–2366S

    PubMed  CAS  Google Scholar 

  99. Cox R, Prescott C, Irving CC (1977) The effect of S adenosylhomocysteine on the DNA methylation in isolated rat liver nuclei. Biochim Biophys Acta 474:493–499

    Article  PubMed  CAS  Google Scholar 

  100. Ghosh AK, Varga J (2007) transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol 213:663–667

    Article  PubMed  CAS  Google Scholar 

  101. Wei JQ, Shehadeh LA, Mitrani JM, Pessanha M, Slepak TI, Webster KA, Bishopric NH (2008) Quantitative control of adaptive cardiac hypertrophy by acetyltransferase p300. Circulation 118:934–946

    Article  PubMed  CAS  Google Scholar 

  102. Huss JM, Kelly DP (2005) Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest 115:547–555

    PubMed  CAS  Google Scholar 

  103. Yang J, Moravec CS, Sussman MA et al (2000) Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation 102:3046–3052

    Article  PubMed  CAS  Google Scholar 

  104. Paolisso G, Gambardella A, Galzerano D et al (1994) Total-body and myocardial substrate oxidation in congestive heart failure. Metabolism 43:174–179

    Article  PubMed  CAS  Google Scholar 

  105. Steenman M, Lamirault G, Le MN, Leger JJ (2005) Gene expression profiling in human cardiovascular disease. Clin Chem Lab Med 43:696–701

    Article  PubMed  CAS  Google Scholar 

  106. Madrazo JA, Kelly DP (2008) The PPAR trio: regulators of myocardial energy metabolism in health and disease. J Mol Cell Cardiol 44:968–975

    Article  PubMed  CAS  Google Scholar 

  107. Wohlschlaeger J, Schmitz KJ, Schmid C et al (2005) Reverse remodeling following insertion of left ventricular assist devices (LVAD): a review of the morphological and molecular changes. Cardiovasc Res 68:376–386

    Article  PubMed  CAS  Google Scholar 

  108. Soppa GK, Barton PJ, Terracciano CM, Yacoub MH (2008) Left ventricular assist device-induced molecular changes in the failing myocardium. Curr Opin Cardiol 23:206–218

    Article  PubMed  Google Scholar 

  109. Kaye DM, Hoshijima M, Chien KR (2008) Reversing advanced heart failure by targeting Ca2+ cycling. Annu Rev Med 59:13–28

    Article  PubMed  CAS  Google Scholar 

  110. Hasenfuss G (1998) Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res 37:279–289

    Article  PubMed  CAS  Google Scholar 

  111. Yano M, Ikeda Y, Matsuzaki M (2005) Altered intracellular Ca2+ handling in heart failure. J Clin Invest 115:556–564

    PubMed  CAS  Google Scholar 

  112. George CH (2008) Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance? Cardiovasc Res 77:302–314

    Article  PubMed  CAS  Google Scholar 

  113. Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92:139–150

    Article  PubMed  CAS  Google Scholar 

  114. Barrans JD, Allen PD, Stamatiou D, Dzau VJ, Liew CC (2002) Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am J Pathol 160:2035–2043

    Article  PubMed  CAS  Google Scholar 

  115. Grzeskowiak R, Witt H, Drungowski M et al (2003) Expression profiling of human idiopathic dilated cardiomyopathy. Cardiovasc Res 59:400–411

    Article  PubMed  CAS  Google Scholar 

  116. Rapundalo ST (1998) Cardiac protein phosphorylation: functional and pathophysiological correlates. Cardiovasc Res 38:559–588

    Article  PubMed  CAS  Google Scholar 

  117. Neumann J, Eschenhagen T, Jones LR, Linck B, Schmitz W, Scholz H, Zimmermann N (1997) Increased expression of cardiac phosphatases in patients with end-stage heart failure. J Mol Cell Cardiol 29:265–272

    Article  PubMed  CAS  Google Scholar 

  118. Carr AN, Schmidt AG, Suzuki Y et al (2002) Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol 22:4124–4135

    Article  PubMed  CAS  Google Scholar 

  119. Peterson JT, Hallak H, Johnson L et al (2001) Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure. Circulation 103:2303–2309

    Article  PubMed  CAS  Google Scholar 

  120. Morita H, Seidman J, Seidman CE (2005) Genetic causes of human heart failure. J Clin Invest 115:518–526

    PubMed  CAS  Google Scholar 

  121. Barry SP, Davidson SM, Townsend PA (2008) Molecular regulation of cardiac hypertrophy. Int J Biochem Cell Biol 40:2023–2039

    Article  PubMed  CAS  Google Scholar 

  122. Blaxall BC, Tschannen-Moran BM, Milano CA, Koch WJ (2003) Differential gene expression and genomic patient stratification following left ventricular assist device support. J Am Coll Cardiol 41:1096–1106

    Article  PubMed  CAS  Google Scholar 

  123. Abraham WT, Gilbert EM, Lowes BD et al (2002) Coordinate changes in Myosin heavy chain isoform gene expression are selectively associated with alterations in dilated cardiomyopathy phenotype. Mol Med 8:750–760

    PubMed  CAS  Google Scholar 

  124. Le CP, Park HY, Rockman HA (2003) Modifier genes and heart failure. Minerva Cardioangiol 51:107–120

    Google Scholar 

  125. Borjesson M, Magnusson Y, Hjalmarson A, Andersson B (2000) A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J 21:1853–1858

    Article  PubMed  CAS  Google Scholar 

  126. Wheeler FC, Fernandez L, Carlson KM, Wolf MJ, Rockman HA, Marchuk DA (2005) QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival. Mamm Genome 16:414–423

    Article  PubMed  CAS  Google Scholar 

  127. van Rooij E, Olson EN (2007) MicroRNAs put their signatures on the heart. Physiol Genomics 31:365–366

    Article  PubMed  CAS  Google Scholar 

  128. McKinsey TA, Olson EN (2005) Toward transcriptional therapies for the failing heart: chemical screens to modulate genes. J Clin Invest 115:538–546

    PubMed  CAS  Google Scholar 

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    José Marín-García MD (Director)

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Correspondence to José Marín-García MD .

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Marín-García, J. (2010). Gene Profiling of the Failing Heart: Epigenetics. In: Heart Failure. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-147-9_3

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  • DOI: https://doi.org/10.1007/978-1-60761-147-9_3

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  • Publisher Name: Humana Press, Totowa, NJ

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  • Online ISBN: 978-1-60761-147-9

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