Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification

Article
  • 84 Downloads

Abstract

Cardiac fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In recent years, despite the underlying mechanisms of cardiac fibrosis are still unknown, numerous studies suggest that epigenetic regulation of cardiac fibrosis. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix protein, a process the epigenetic machinery plays a pivotal role. Epigenetic modifications contain three main processes: DNA methylation, histone modifications, and noncoding RNAs. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of molecule mechanisms that target epigenetic regulators as a means of treating cardiac fibrosis.

Keywords

Cardiac fibrosis Epigenetic DNA methylation Noncoding RNA Histone modification 

Abbreviations

miRs

MicroRNAs

LncRNA

Long noncoding RNA

ncRNAs

Noncoding RNAs

α-SMA

α-smooth muscle actin

ECM

Extracellular matrix

RNAi

RNA interference

DNMTs

DNA methyltransferases

HAT

Histone acetyl transferase

HDAC

Histone deacetylase

HCM

Hypertrophic cardiomyopathy

DBcAMP

cAMP analog N(6),2’-O-dibutyryladenosine 3′,5′-cyclic monophosphate

MeCP2

Methyl CpG binding protein 2

CpG

CpG island

RASAL1

RAS protein activator like-1

Ras-GTP

RAS GTPase activating protein

MI

Myocardial infarction

RAAS

Renin-angiotensin-aldosterone system

MMP

Maladjustment of matrix metalloproteinases

EMT

Epithelial mesenchymal transition

TGF-β

Transforming growth factor beta

DUSP5

Dual-specificity phosphatase 5

SHR

Spontaneously hypertensive rat

EndMT

Endothelial mesenchymal transition

RASSF1A

Ras association domain family 1 isoform A

TET

Ten eleven translocation

TSA

Trichostatin A

VPA

Valproic acid

MR

Mineralocorticoid receptor

MRTF-A

Myocardin-related transcription factor A

Ang II

Angiotensin II

EZH1

Enhancer of zeste homolog 1

TFIID

Transcription factor II D

Notes

Acknowledgements

This project was supported by the National Natural Science Foundation of China (81700212, 81570295) and Natural Science Foundation of Anhui Provincial Education Department (KJ2017A168).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Shimada-Sugimoto M, Otowa T, Miyagawa T, Umekage T, Kawamura Y, Bundo M, Iwamoto K, Tochigi M, Kasai K, Kaiya H, Tanii H, Okazaki Y, Tokunaga K, Sasaki T (2017) Epigenome-wide association study of DNA methylation in panic disorder. Clin Epigenetics 9:6.  https://doi.org/10.1186/s13148-016-0307-1 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Zam W, Khadour A (2017) Impact of phytochemicals and dietary patterns on epigenome and cancer. Nutr Cancer 69(2):184–200.  https://doi.org/10.1080/01635581.2017.1263746 CrossRefPubMedGoogle Scholar
  3. 3.
    Zhang Y, Ren J (2016) Epigenetics and obesity cardiomyopathy: from pathophysiology to prevention and management. Pharmacol Ther 161:52–66.  https://doi.org/10.1016/j.pharmthera.2016.03.005 CrossRefPubMedGoogle Scholar
  4. 4.
    Rodriguez-Rodero S, Delgado-Alvarez E, Diaz-Naya L, Martin Nieto A, Menendez Torre E (2017) Epigenetic modulators of thyroid cancer. Endocrinol Diabetes Nutr 64(1):44–56.  https://doi.org/10.1016/j.endinu.2016.09.006 CrossRefPubMedGoogle Scholar
  5. 5.
    Satoh A, Niwano S, Niwano H, Kishihara J, Aoyama Y, Oikawa J, Fukaya H, Tamaki H, Ako J (2017) Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation. Heart Vessel 32(1):90–100.  https://doi.org/10.1007/s00380-016-0874-2 CrossRefGoogle Scholar
  6. 6.
    Stratton MS, McKinsey TA (2016) Epigenetic regulation of cardiac fibrosis. J Mol Cell Cardiol 92:206–213.  https://doi.org/10.1016/j.yjmcc.2016.02.011 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tao H, Yang JJ, Shi KH (2015) Non-coding RNAs as direct and indirect modulators of epigenetic mechanism regulation of cardiac fibrosis. Expert Opin Ther Targets 19(5):707–716.  https://doi.org/10.1517/14728222.2014.1001740 CrossRefPubMedGoogle Scholar
  8. 8.
    Yu LM, Xu Y (2015) Epigenetic regulation in cardiac fibrosis. World J Cardiol 7(11):784–791.  https://doi.org/10.4330/wjc.v7.i11.784 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Feng B, Cao Y, Chen S, Chu X, Chu Y, Chakrabarti S (2016) miR-200b mediates endothelial-to-mesenchymal transition in diabetic cardiomyopathy. Diabetes 65(3):768–779.  https://doi.org/10.2337/db15-1033 CrossRefPubMedGoogle Scholar
  10. 10.
    Gyongyosi M, Winkler J, Ramos I, Do QT, Firat H, McDonald K, Gonzalez A, Thum T, Diez J, Jaisser F, Pizard A, Zannad F (2017) Myocardial fibrosis: biomedical research from bench to bedside. Eur J Heart Fail 19(2):177–191.  https://doi.org/10.1002/ejhf.696 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Riaz S, Zeidan A, Mraiche F (2017) Myocardial proteases and cardiac remodeling. J Cell Physiol 232:3244–3250.  https://doi.org/10.1002/jcp.25884 CrossRefPubMedGoogle Scholar
  12. 12.
    Mewhort HE, Lipon BD, Svystonyuk DA, Teng G, Guzzardi DG, Silva C, Yong VW, Fedak PW (2016) Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-beta1. Am J Phys Heart Circ Phys 310(6):H716–H724.  https://doi.org/10.1152/ajpheart.00309.2015 Google Scholar
  13. 13.
    Tallquist MD, Molkentin JD (2017) Redefining the identity of cardiac fibroblasts. Nat Rev Cardiol 14:484–491.  https://doi.org/10.1038/nrcardio.2017.57 CrossRefPubMedGoogle Scholar
  14. 14.
    Takawale A, Zhang P, Patel VB, Wang X, Oudit G, Kassiri Z (2017) Tissue inhibitor of matrix metalloproteinase-1 promotes myocardial fibrosis by mediating CD63-integrin beta1 interaction. Hypertension 69:1092–1103.  https://doi.org/10.1161/HYPERTENSIONAHA.117.09045 CrossRefPubMedGoogle Scholar
  15. 15.
    Bollong MJ, Yang B, Vergani N, Beyer BA, Chin EN, Zambaldo C, Wang D, Chatterjee AK, Lairson LL, Schultz PG (2017) Small molecule-mediated inhibition of myofibroblast transdifferentiation for the treatment of fibrosis. Proc Natl Acad Sci U S A 114:4679–4684.  https://doi.org/10.1073/pnas.1702750114 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Prabhu SD, Frangogiannis NG (2016) The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis. Circ Res 119(1):91–112.  https://doi.org/10.1161/CIRCRESAHA.116.303577 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Sag CM, Schnelle M, Zhang J, Murdoch CE, Kossmann S, Protti A, Santos CX, Sawyer GJ, Zhang X, Mongue-Din H, Richards DA, Brewer AC, Prysyazhna O, Maier LS, Wenzel P, Eaton PJ, Shah AM (2017) Distinct regulatory effects of myeloid cell and endothelial cell Nox2 on blood pressure. Circulation 135:2163–2177.  https://doi.org/10.1161/CIRCULATIONAHA.116.023877 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Seeger T, Xu QF, Muhly-Reinholz M, Fischer A, Kremp EM, Zeiher AM, Dimmeler S (2016) Inhibition of let-7 augments the recruitment of epicardial cells and improves cardiac function after myocardial infarction. J Mol Cell Cardiol 94:145–152.  https://doi.org/10.1016/j.yjmcc.2016.04.002 CrossRefPubMedGoogle Scholar
  19. 19.
    De Cecco CN, Muscogiuri G, Varga-Szemes A, Schoepf UJ (2017) Cutting edge clinical applications in cardiovascular magnetic resonance. World J Radiol 9(1):1–4.  https://doi.org/10.4329/wjr.v9.i1.1 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ambrosi C, Manzo M, Baubec T (2017) Dynamics and context-dependent roles of DNA methylation. J Mol Biol 429:1459–1475.  https://doi.org/10.1016/j.jmb.2017.02.008 CrossRefPubMedGoogle Scholar
  21. 21.
    Parrilla-Doblas JT, Ariza RR, Roldan-Arjona T (2017) Targeted DNA demethylation in human cells by fusion of a plant 5-methylcytosine DNA glycosylase to a sequence-specific DNA binding domain. Epigenetics 12(4):296–303.  https://doi.org/10.1080/15592294.2017.1294306 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Amort T, Lusser A (2017) Detection of 5-methylcytosine in specific poly(A) RNAs by bisulfite sequencing. Methods Mol Biol 1562:107–121.  https://doi.org/10.1007/978-1-4939-6807-7_8 CrossRefPubMedGoogle Scholar
  23. 23.
    Singh VB, Sribenja S, Wilson KE, Attwood KM, Hillman JC, Pathak S, Higgins MJ (2017) Blocked transcription through KvDMR1 results in absence of methylation and gene silencing resembling Beckwith-Wiedemann syndrome. Development 144:1820–1830.  https://doi.org/10.1242/dev.145136 CrossRefPubMedGoogle Scholar
  24. 24.
    Agorio A, Durand S, Fiume E, Brousse C, Gy I, Simon M, Anava S, Rechavi O, Loudet O, Camilleri C, Bouche N (2017) An arabidopsis natural epiallele maintained by a feed-forward silencing loop between histone and DNA. PLoS Genet 13(1):e1006551.  https://doi.org/10.1371/journal.pgen.1006551 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Blevins T, Wang J, Pflieger D, Pontvianne F, Pikaard CS (2017) Hybrid incompatibility caused by an epiallele. Proc Natl Acad Sci U S A 114(14):3702–3707.  https://doi.org/10.1073/pnas.1700368114 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Chen C, Wang L, Chen S, Wu X, Gu M, Chen X, Jiang S, Wang Y, Deng Z, Dedon PC, Chen S (2017) Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes. Proc Natl Acad Sci U S A 114:4501–4506.  https://doi.org/10.1073/pnas.1702450114 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Scott H, Smith AE, Barker GR, Uney JB, Warburton EC (2017) Contrasting roles for DNA methyltransferases and histone deacetylases in single-item and associative recognition memory. Neuroepigenetics 9:1–9.  https://doi.org/10.1016/j.nepig.2017.02.001 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mendonca A, Sanchez OF, Liu W, Li Z, Yuan C (2017) CpG dinucleotide positioning patterns determine the binding affinity of methyl-binding domain to nucleosomes. Biochim Biophys Acta 1860:713–720.  https://doi.org/10.1016/j.bbagrm.2017.03.006 CrossRefPubMedGoogle Scholar
  29. 29.
    Sassa A, Kanemaru Y, Kamoshita N, Honma M, Yasui M (2016) Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome. Genes Environ 38(1):17.  https://doi.org/10.1186/s41021-016-0045-9 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yet I, Tsai PC, Castillo-Fernandez JE, Carnero-Montoro E, Bell JT (2016) Genetic and environmental impacts on DNA methylation levels in twins. Epigenomics 8(1):105–117.  https://doi.org/10.2217/epi.15.90 CrossRefPubMedGoogle Scholar
  31. 31.
    Benesova M, Trejbalova K, Kucerova D, Vernerova Z, Hron T, Szabo A, Amouroux R, Klezl P, Hajkova P, Hejnar J (2017) Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation. Mol Carcinog 56:1837–1850.  https://doi.org/10.1002/mc.22638 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Chen C, Li R, Ross RS, Manso AM (2016) Integrins and integrin-related proteins in cardiac fibrosis. J Mol Cell Cardiol 93:162–174.  https://doi.org/10.1016/j.yjmcc.2015.11.010 CrossRefPubMedGoogle Scholar
  33. 33.
    Grimaldi V, De Pascale MR, Zullo A, Soricelli A, Infante T, Mancini FP, Napoli C (2017) Evidence of epigenetic tags in cardiac fibrosis. J Cardiol 69(2):401–408.  https://doi.org/10.1016/j.jjcc.2016.10.004 CrossRefPubMedGoogle Scholar
  34. 34.
    Jeong HY, Kang WS, Hong MH, Jeong HC, Shin MG, Jeong MH, Kim YS, Ahn Y (2015) 5-Azacytidine modulates interferon regulatory factor 1 in macrophages to exert a cardioprotective effect. Sci Rep 5:15768.  https://doi.org/10.1038/srep15768 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Salim T, Sershen CL, May EE (2016) Investigating the role of TNF-alpha and IFN-gamma activation on the dynamics of iNOS gene expression in LPS stimulated macrophages. PLoS One 11(6):e0153289.  https://doi.org/10.1371/journal.pone.0153289 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lv T, Du Y, Cao N, Zhang S, Gong Y, Bai Y, Wang W, Liu H (2016) Proliferation in cardiac fibroblasts induced by beta1-adrenoceptor autoantibody and the underlying mechanisms. Sci Rep 6:32430.  https://doi.org/10.1038/srep32430 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Fang X, Robinson J, Wang-Hu J, Jiang L, Freeman DA, Rivkees SA, Wendler CC (2015) cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes. Am J Physiol Cell Physiol 309(6):C425–C436.  https://doi.org/10.1152/ajpcell.00058.2015 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Spitler KM, Ponce JM, Oudit GY, Hall DD, Grueter CE (2017) Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming. Am J Phys Heart Circ Phys 312(4):H768–H780.  https://doi.org/10.1152/ajpheart.00728.2016 Google Scholar
  39. 39.
    Mayer SC, Gilsbach R, Preissl S, Monroy Ordonez EB, Schnick T, Beetz N, Lother A, Rommel C, Ihle H, Bugger H, Ruhle F, Schrepper A, Schwarzer M, Heilmann C, Bonisch U, Gupta SK, Wilpert J, Kretz O, von Elverfeldt D, Orth J, Aktories K, Beyersdorf F, Bode C, Stiller B, Kruger M, Thum T, Doenst T, Stoll M, Hein L (2015) Adrenergic repression of the epigenetic reader MeCP2 facilitates cardiac adaptation in chronic heart failure. Circ Res 117(7):622–633.  https://doi.org/10.1161/CIRCRESAHA.115.306721 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Tao H, Yang JJ, Hu W, Shi KH, Deng ZY, Li J (2016) MeCP2 regulation of cardiac fibroblast proliferation and fibrosis by down-regulation of DUSP5. Int J Biol Macromol 82:68–75.  https://doi.org/10.1016/j.ijbiomac.2015.10.076 CrossRefPubMedGoogle Scholar
  41. 41.
    Davis JM 3rd, Lin G, Oh JK, Crowson CS, Achenbach SJ, Therneau TM, Matteson EL, Rodeheffer RJ, Gabriel SE (2017) Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol 240:379–385.  https://doi.org/10.1016/j.ijcard.2017.03.108 CrossRefPubMedGoogle Scholar
  42. 42.
    Stenzig J, Hirt MN, Loser A, Bartholdt LM, Hensel JT, Werner TR, Riemenschneider M, Indenbirken D, Guenther T, Muller C, Hubner N, Stoll M, Eschenhagen T (2016) DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors. Basic Res Cardiol 111(1):9.  https://doi.org/10.1007/s00395-015-0528-z CrossRefPubMedGoogle Scholar
  43. 43.
    Watson CJ, Horgan S, Neary R, Glezeva N, Tea I, Corrigan N, McDonald K, Ledwidge M, Baugh J (2016) Epigenetic therapy for the treatment of hypertension-induced cardiac hypertrophy and fibrosis. J Cardiovasc Pharmacol Ther 21(1):127–137.  https://doi.org/10.1177/1074248415591698 CrossRefPubMedGoogle Scholar
  44. 44.
    Singh P, O'Connell M, Shubhashish S (2016) Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications. Stem cell Invest 3:51.  https://doi.org/10.21037/sci.2016.09.07 CrossRefGoogle Scholar
  45. 45.
    Xu X, Tan X, Tampe B, Nyamsuren G, Liu X, Maier LS, Sossalla S, Kalluri R, Zeisberg M, Hasenfuss G, Zeisberg EM (2015) Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis. Cardiovasc Res 105(3):279–291.  https://doi.org/10.1093/cvr/cvv015 CrossRefPubMedGoogle Scholar
  46. 46.
    Tao H, Yang JJ, Chen ZW, Xu SS, Zhou X, Zhan HY, Shi KH (2014) DNMT3A silencing RASSF1A promotes cardiac fibrosis through upregulation of ERK1/2. Toxicology 323:42–50.  https://doi.org/10.1016/j.tox.2014.06.006 CrossRefPubMedGoogle Scholar
  47. 47.
    Takamura M, Kurokawa K, Ootsuji H, Inoue O, Okada H, Nomura A, Kaneko S, Usui S (2017) Long-term administration of eicosapentaenoic acid improves post-myocardial infarction cardiac remodeling in mice by regulating macrophage polarization. J Am Heart Assoc 6(2):e004560.  https://doi.org/10.1161/JAHA.116.004560 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Watson CJ, Collier P, Tea I, Neary R, Watson JA, Robinson C, Phelan D, Ledwidge MT, McDonald KM, McCann A, Sharaf O, Baugh JA (2014) Hypoxia-induced epigenetic modifications are associated with cardiac tissue fibrosis and the development of a myofibroblast-like phenotype. Hum Mol Genet 23(8):2176–2188.  https://doi.org/10.1093/hmg/ddt614 CrossRefPubMedGoogle Scholar
  49. 49.
    Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang SS, Zhi H, Qin F, Jacobsen DW, Loscalzo J, Joseph J (2012) Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res 56(12):1812–1824.  https://doi.org/10.1002/mnfr.201200386 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Nagai S, Davis RE, Mattei PJ, Eagen KP, Kornberg RD (2017) Chromatin potentiates transcription. Proc Natl Acad Sci U S A 114(7):1536–1541.  https://doi.org/10.1073/pnas.1620312114 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Wilson MD, Benlekbir S, Fradet-Turcotte A, Sherker A, Julien JP, McEwan A, Noordermeer SM, Sicheri F, Rubinstein JL, Durocher D (2016) The structural basis of modified nucleosome recognition by 53BP1. Nature 536(7614):100–103.  https://doi.org/10.1038/nature18951 CrossRefPubMedGoogle Scholar
  52. 52.
    Leung A, Trac C, Du J, Natarajan R, Schones DE (2016) Persistent chromatin modifications induced by high fat diet. J Biol Chem 291(20):10446–10455.  https://doi.org/10.1074/jbc.M115.711028 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Taberlay PC, Achinger-Kawecka J, Lun AT, Buske FA, Sabir K, Gould CM, Zotenko E, Bert SA, Giles KA, Bauer DC, Smyth GK, Stirzaker C, O'Donoghue SI, Clark SJ (2016) Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations. Genome Res 26(6):719–731.  https://doi.org/10.1101/gr.201517.115 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Bauer AJ, Martin KA (2017) Coordinating regulation of gene expression in cardiovascular disease: interactions between chromatin modifiers and transcription factors. Front Cardiovasc Med 4:19.  https://doi.org/10.3389/fcvm.2017.00019 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Filgueiras LR, Brandt SL, Ramalho TR, Jancar S, Serezani CH (2017) Imbalance between HDAC and HAT activities drives aberrant STAT1/MyD88 expression in macrophages from type 1 diabetic mice. J Diabetes Complicat 31(2):334–339.  https://doi.org/10.1016/j.jdiacomp.2016.08.001 CrossRefPubMedGoogle Scholar
  56. 56.
    Ji S, Zhu L, Gao Y, Zhang X, Yan Y, Cen J, Li R, Zeng R, Liao L, Hou C, Gao Y, Gao S, Wei G, Hui L (2017) Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening. Cell Res 27:642–656.  https://doi.org/10.1038/cr.2017.36 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Meyners C, Mertens M, Wessig P, Meyer-Almes FJ (2017) A fluorescence-lifetime-based binding assay for class IIa histone deacetylases. Chemistry 23(13):3107–3116.  https://doi.org/10.1002/chem.201605140 CrossRefPubMedGoogle Scholar
  58. 58.
    Di Giorgio E, Franforte E, Cefalu S, Rossi S, Dei Tos AP, Brenca M, Polano M, Maestro R, Paluvai H, Picco R, Brancolini C (2017) The co-existence of transcriptional activator and transcriptional repressor MEF2 complexes influences tumor aggressiveness. PLoS Genet 13(4):e1006752.  https://doi.org/10.1371/journal.pgen.1006752 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Mahendrarajah N, Paulus R, Kramer OH (2016) Histone deacetylase inhibitors induce proteolysis of activated CDC42-associated kinase-1 in leukemic cells. J Cancer Res Clin Oncol 142(11):2263–2273.  https://doi.org/10.1007/s00432-016-2229-x CrossRefPubMedGoogle Scholar
  60. 60.
    Li RF, Cao SS, Fang WJ, Song Y, Luo XT, Wang HY, Wang JG (2017) Roles of HDAC2 and HDAC8 in cardiac remodeling in renovascular hypertensive rats and the effects of valproic acid sodium. Pharmacology 99(1–2):27–39.  https://doi.org/10.1159/000449467 CrossRefPubMedGoogle Scholar
  61. 61.
    Yu L, Yang G, Weng X, Liang P, Li L, Li J, Fan Z, Tian W, Wu X, Xu H, Fang M, Ji Y, Li Y, Chen Q, Xu Y (2015) Histone methyltransferase SET1 mediates angiotensin II-induced endothelin-1 transcription and cardiac hypertrophy in mice. Arterioscler Thromb Vasc Biol 35(5):1207–1217.  https://doi.org/10.1161/ATVBAHA.115.305230 CrossRefPubMedGoogle Scholar
  62. 62.
    Barreiro E, Tajbakhsh S (2017) Epigenetic regulation of muscle development. J Muscle Res Cell Motil 38:31–35.  https://doi.org/10.1007/s10974-017-9469-5 CrossRefPubMedGoogle Scholar
  63. 63.
    Zhang M, Liu H, Gao Y, Zhu Z, Chen Z, Zheng P, Xue L, Li J, Teng M, Niu L (2016) Structural insights into the association of Hif1 with histones H2A-H2B dimer and H3-H4 tetramer. Structure 24(10):1810–1820.  https://doi.org/10.1016/j.str.2016.08.001 CrossRefPubMedGoogle Scholar
  64. 64.
    Wu Z, Connolly J, Biggar KK (2017) Beyond histones: the expanding roles of protein lysine methylation. FEBS J 284:2732–2744.  https://doi.org/10.1111/febs.14056 CrossRefPubMedGoogle Scholar
  65. 65.
    Harr JC, Gonzalez-Sandoval A, Gasser SM (2016) Histones and histone modifications in perinuclear chromatin anchoring: from yeast to man. EMBO Rep 17(2):139–155.  https://doi.org/10.15252/embr.201541809 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Kim H, Ramirez CN, Su ZY, Kong AN (2016) Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells. J Nutr Biochem 33:54–62.  https://doi.org/10.1016/j.jnutbio.2015.09.014 CrossRefPubMedGoogle Scholar
  67. 67.
    Ahmadi M, Gharibi T, Dolati S, Rostamzadeh D, Aslani S, Baradaran B, Younesi V, Yousefi M (2017) Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases. Biomed Pharmacother 87:596–608.  https://doi.org/10.1016/j.biopha.2016.12.072 CrossRefPubMedGoogle Scholar
  68. 68.
    Luo T, Chen B, Wang X (2015) 4-PBA prevents pressure overload-induced myocardial hypertrophy and interstitial fibrosis by attenuating endoplasmic reticulum stress. Chem Biol Interact 242:99–106.  https://doi.org/10.1016/j.cbi.2015.09.025 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Pinkerneil M, Hoffmann MJ, Schulz WA, Niegisch G (2017) HDACs and HDAC inhibitors in urothelial carcinoma—perspectives for an antineoplastic treatment. Curr Med Chem (in press)Google Scholar
  70. 70.
    Schuetze KB, Stratton MS, Blakeslee WW, Wempe MF, Wagner FF, Holson EB, Kuo YM, Andrews AJ, Gilbert TM, Hooker JM, McKinsey TA (2017) Overlapping and divergent actions of structurally distinct histone deacetylase inhibitors in cardiac fibroblasts. J Pharmacol Exp Ther 361(1):140–150.  https://doi.org/10.1124/jpet.116.237701 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Wang WW, Han JH, Wang L, Bao TH (2017) Scutellarin may alleviate cognitive deficits in a mouse model of hypoxia by promoting proliferation and neuronal differentiation of neural stem cells. Iran J Basic Med Sci 20(3):272–279.  https://doi.org/10.22038/IJBMS.2017.8355 PubMedPubMedCentralGoogle Scholar
  72. 72.
    Tao H, Yang JJ, Shi KH, Li J (2016) Epigenetic factors MeCP2 and HDAC6 control alpha-tubulin acetylation in cardiac fibroblast proliferation and fibrosis. Inflamm Res 65(5):415–426.  https://doi.org/10.1007/s00011-016-0925-2 CrossRefPubMedGoogle Scholar
  73. 73.
    Chen Y, Du J, Zhao YT, Zhang L, Lv G, Zhuang S, Qin G, Zhao TC (2015) Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice. Cardiovasc Diabetol 14:99.  https://doi.org/10.1186/s12933-015-0262-8 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    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(5):782–791.  https://doi.org/10.1124/mol.114.096974 CrossRefPubMedGoogle Scholar
  75. 75.
    Seok YM, Lee HA, Park KM, Hwangbo MH, Kim IK (2016) Lysine deacetylase inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptor instead of histone acetylation in spontaneously hypertensive rats. Naunyn Schmiedeberg's Arch Pharmacol 389(7):799–808.  https://doi.org/10.1007/s00210-016-1246-2 CrossRefGoogle Scholar
  76. 76.
    Weng X, Yu L, Liang P, Li L, Dai X, Zhou B, Wu X, Xu H, Fang M, Chen Q, Xu Y (2015) A crosstalk between chromatin remodeling and histone H3K4 methyltransferase complexes in endothelial cells regulates angiotensin II-induced cardiac hypertrophy. J Mol Cell Cardiol 82:48–58.  https://doi.org/10.1016/j.yjmcc.2015.02.010 CrossRefPubMedGoogle Scholar
  77. 77.
    Weng X, Yu L, Liang P, Chen D, Cheng X, Yang Y, Li L, Zhang T, Zhou B, Wu X, Xu H, Fang M, Gao Y, Chen Q, Xu Y (2015) Endothelial MRTF-A mediates angiotensin II induced cardiac hypertrophy. J Mol Cell Cardiol 80:23–33.  https://doi.org/10.1016/j.yjmcc.2014.11.009 CrossRefPubMedGoogle Scholar
  78. 78.
    Leus NG, van den Bosch T, van der Wouden PE, Krist K, Ourailidou ME, Eleftheriadis N, Kistemaker LE, Bos S, Gjaltema RA, Mekonnen SA, Bischoff R, Gosens R, Haisma HJ, Dekker FJ (2017) HDAC1-3 inhibitor MS-275 enhances IL10 expression in RAW264.7 macrophages and reduces cigarette smoke-induced airway inflammation in mice. Sci Rep 7:45047.  https://doi.org/10.1038/srep45047 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Iyer A, Fenning A, Lim J, Le GT, Reid RC, Halili MA, Fairlie DP, Brown L (2010) Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats. Br J Pharmacol 159(7):1408–1417.  https://doi.org/10.1111/j.1476-5381.2010.00637.x CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Zhang J, Wang P, Wan L, Xu S, Pang D (2017) The emergence of noncoding RNAs as Heracles in autophagy. Autophagy 13:1004–1024.  https://doi.org/10.1080/15548627.2017.1312041 CrossRefPubMedGoogle Scholar
  81. 81.
    da Rocha ST, Heard E (2017) Novel players in X inactivation: insights into Xist-mediated gene silencing and chromosome conformation. Nat Struct Mol Biol 24(3):197–204.  https://doi.org/10.1038/nsmb.3370 CrossRefPubMedGoogle Scholar
  82. 82.
    Zapata JC, Campilongo F, Barclay RA, DeMarino C, Iglesias-Ussel MD, Kashanchi F, Romerio F (2017) The human immunodeficiency virus 1 ASP RNA promotes viral latency by recruiting the polycomb repressor complex 2 and promoting nucleosome assembly. Virology 506:34–44.  https://doi.org/10.1016/j.virol.2017.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Liu X, Liu S (2017) Role of microRNAs in the pathogenesis of diabetic cardiomyopathy. Biomed Rep 6(2):140–145.  https://doi.org/10.3892/br.2017.841 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Wang A, Kwee LC, Grass E, Neely ML, Gregory SG, Fox KAA, Armstrong PW, White HD, Ohman EM, Roe MT, Shah SH, Chan MY (2017) Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome. Atherosclerosis 261:19–25.  https://doi.org/10.1016/j.atherosclerosis.2017.03.041 CrossRefPubMedGoogle Scholar
  85. 85.
    Pitchiaya S, Heinicke LA, Park JI, Cameron EL, Walter NG (2017) Resolving subcellular miRNA trafficking and turnover at single-molecule resolution. Cell Rep 19(3):630–642.  https://doi.org/10.1016/j.celrep.2017.03.075 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Heery R, Finn SP, Cuffe S, Gray SG (2017) Long non-coding RNAs: key regulators of epithelial-mesenchymal transition, tumour drug resistance and cancer stem cells. Cancers 9(4).  https://doi.org/10.3390/cancers9040038
  87. 87.
    Han D, Gao Q, Cao F (2017) Long noncoding RNAs (LncRNAs)—the dawning of a new treatment for cardiac hypertrophy and heart failure. Biochim Biophys Acta 1863:2078–2084.  https://doi.org/10.1016/j.bbadis.2017.02.024 CrossRefPubMedGoogle Scholar
  88. 88.
    Liu H, Shang X, Zhu H (2017) LncRNA/DNA binding analysis reveals losses and gains and lineage specificity of genomic imprinting in mammals. Bioinformatics 33(10):1431–1436.  https://doi.org/10.1093/bioinformatics/btw818
  89. 89.
    Hirschi A, Martin WJ, Luka Z, Loukachevitch LV, Reiter NJ (2016) G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme. RNA 22(8):1250–1260.  https://doi.org/10.1261/rna.057265.116 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Mazidi M, Penson P, Gluba-Brzozka A, Rysz J, Banach M (2017) Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease. J Clinical Lipidol 11:617–623.  https://doi.org/10.1016/j.jacl.2017.03.009 CrossRefGoogle Scholar
  91. 91.
    Qu X, Song X, Yuan W, Shu Y, Wang Y, Zhao X, Gao M, Lu R, Luo S, Zhao W, Zhang Y, Sun L, Lu Y (2016) Expression signature of lncRNAs and their potential roles in cardiac fibrosis of post-infarct mice. Biosci Rep 36(3).  https://doi.org/10.1042/BSR20150278
  92. 92.
    Tao H, Cao W, Yang JJ, Shi KH, Zhou X, Liu LP, Li J (2016) Long noncoding RNA H19 controls DUSP5/ERK1/2 axis in cardiac fibroblast proliferation and fibrosis. Cardiovascular Pathol 25(5):381–389.  https://doi.org/10.1016/j.carpath.2016.05.005 CrossRefGoogle Scholar
  93. 93.
    Peters T, Hermans-Beijnsberger S, Beqqali A, Bitsch N, Nakagawa S, Prasanth KV, de Windt LJ, van Oort RJ, Heymans S, Schroen B (2016) Long non-coding RNA Malat-1 is dispensable during pressure overload-induced cardiac remodeling and failure in mice. PLoS One 11(2):e0150236.  https://doi.org/10.1371/journal.pone.0150236 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Jiang X, Zhang F, Ning Q (2015) Losartan reverses the down-expression of long noncoding RNA-NR024118 and Cdkn1c induced by angiotensin II in adult rat cardiac fibroblasts. Pathol Biol 63(3):122–125.  https://doi.org/10.1016/j.patbio.2015.04.001 CrossRefPubMedGoogle Scholar
  95. 95.
    Jiang XY, Ning QL (2014) Expression profiling of long noncoding RNAs and the dynamic changes of lncRNA-NR024118 and Cdkn1c in angiotensin II-treated cardiac fibroblasts. Int J Clin Exp Pathol 7(4):1325–1336PubMedPubMedCentralGoogle Scholar
  96. 96.
    Tao L, Bei Y, Chen P, Lei Z, Fu S, Zhang H, Xu J, Che L, Chen X, Sluijter JP, Das S, Cretoiu D, Xu B, Zhong J, Xiao J, Li X (2016) Crucial role of miR-433 in regulating cardiac fibrosis. Theranostics 6(12):2068–2083.  https://doi.org/10.7150/thno.15007 CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Du W, Liang H, Gao X, Li X, Zhang Y, Pan Z, Li C, Wang Y, Liu Y, Yuan W, Ma N, Chu W, Shan H, Lu Y (2016) MicroRNA-328, a potential anti-fibrotic target in cardiac interstitial fibrosis. Cell Physiol Biochem 39(3):827–836.  https://doi.org/10.1159/000447793 CrossRefPubMedGoogle Scholar
  98. 98.
    Piletic K, Kunej T (2016) MicroRNA epigenetic signatures in human disease. Arch Toxicol 90(10):2405–2419.  https://doi.org/10.1007/s00204-016-1815-7 CrossRefPubMedGoogle Scholar
  99. 99.
    Belleville-Rolland T, Sassi Y, Decouture B, Dreano E, Hulot JS, Gaussem P, Bachelot-Loza C (2016) MRP4 (ABCC4) as a potential pharmacologic target for cardiovascular disease. Pharmacol Res 107:381–389.  https://doi.org/10.1016/j.phrs.2016.04.002 CrossRefPubMedGoogle Scholar
  100. 100.
    Xu Z, Sun J, Tong Q, Lin Q, Qian L, Park Y, Zheng Y (2016) The role of ERK1/2 in the development of diabetic cardiomyopathy. Int J Mol Sci 17(12).  https://doi.org/10.3390/ijms17122001
  101. 101.
    Renaud L, Harris LG, Mani SK, Kasiganesan H, Chou JC, Baicu CF, Van Laer A, Akerman AW, Stroud RE, Jones JA, Zile MR, Menick DR (2015) HDACs regulate miR-133a expression in pressure overload-induced cardiac fibrosis. Circ Heart Fail 8(6):1094–1104.  https://doi.org/10.1161/CIRCHEARTFAILURE.114.001781 PubMedPubMedCentralGoogle Scholar
  102. 102.
    Zhu WS, Tang CM, Xiao Z, Zhu JN, Lin QX, Fu YH, Hu ZQ, Zhang Z, Yang M, Zheng XL, Wu SL, Shan ZX (2016) Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts. Oncotarget 7(48):78331–78342.  https://doi.org/10.18632/oncotarget.13048 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Takawale A, Sakamuri SS, Kassiri Z (2015) Extracellular matrix communication and turnover in cardiac physiology and pathology. Compr Physiol 5(2):687–719.  https://doi.org/10.1002/cphy.c140045 CrossRefPubMedGoogle Scholar
  104. 104.
    Jia G, Jia Y, Sowers JR (2016) Role of mineralocorticoid receptor activation in cardiac diastolic dysfunction. Biochim Biophys Acta 1863:2012–2018.  https://doi.org/10.1016/j.bbadis.2016.10.025 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Basic Medical Sciences and Clinical PharmacyChina Pharmaceutical UniversityNanjingChina
  2. 2.Department of Cardiothoracic Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina
  3. 3.Department of PharmacologyThe Second Hospital of Anhui Medical UniversityHefeiChina
  4. 4.School of pharmacyAnhui Medical UniversityHefeiChina

Personalised recommendations