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Reactive Oxygen Species and Their Epigenetic Consequences in Heart Diseases

  • Seema Bhargava
Chapter

Abstract

Highly reactive molecules with an unpaired electron are known as free radicals. They collide with other molecules and set up a chain reaction by either passing on the unpaired electron to the neighbouring molecule or getting quenched by it. In biological systems, the most damaging free radicals are the oxygen radicals – also termed as the reactive oxygen species [ROS] – namely superoxide, hydroxyl, and perhydroxyl. Oxidation/peroxidation of lipids, DNA bases and structural membranes through these radicals results in different pathological events depending on the site of oxidation.

These radicals are derived mostly from within our body through several well-known mechanisms, and, to counter their effects, the body has a well-established anti-oxidant system. In physiological situations, the two are in equilibrium. However, when there is an imbalance between these oxidants and anti-oxidants, pathology results.

Of all tissues, the myocardium is the most susceptible to oxidative damage as they harbour a high density of mitochondria, the powerhouses of the cells wherein oxidative phosphorylation occurs. One of the mechanisms of oxidative pathology is through epigenetic modifications, the three major types of epigenetic mechanisms being methylation/demethylation, acetylation/de-acetylation and histone modification. Whichever mechanism is involved, the result is altered gene expression. This may occur in the embryo, the fetus, the infant or the adult. At each stage, the consequences are different.

Broadly speaking, epigenetic modifications during early cardiac development lead to structural deformities, whereas these modifications occurring during later development of the heart result in conduction abnormalities and arrhythmias, coronary artery malformations and valvular defects. When oxidative damage occurs later in life, the result can be arrhythmias, hypertrophic cardiomyopathies, congestive cardiac failure and myocardial infarction. Lipid peroxidation coupled with oxidative damage to the basement membrane of blood vessels leads to coronary artery remodelling with resultant atherothrombosis and myocardial infarction.

This chapter details the mechanisms involved and the possible therapeutic implications thereof.

Keywords

Oxidant Antioxidant Cardiomyopathy Atherothrombosis Epigenetics 

References

  1. 1.
    Bender D (2015) Free radicals and antioxidant nutrients. In: Rodwell VW, Kennelly PJ, Bender DA, Weil PA, Botham KM (eds) Harper’s illustrated biochemistry, 13th edn. McGraw Hill, New YorkGoogle Scholar
  2. 2.
    Iles KE, Forman HJ (2002) Macrophage signalling and respiratory burst. Immunol Res 26(1–3):95–105CrossRefGoogle Scholar
  3. 3.
    Kietzmann T, Petri A, Shvetsova A, Gerhold JM, Gorlach A (2017) The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol 174:1533–1554CrossRefGoogle Scholar
  4. 4.
    Petry A, Weitnauer M, Gorlach A (2010) Receptor activation of NADPH oxidases. Antioxid Redox Signal 13:467–487CrossRefGoogle Scholar
  5. 5.
    Gao S, Li C, Chen L, Zhou X (2017) Actions and mechanisms of reactive oxygen species and oxidative system in semen. Mol Cell Toxicol 13:143–154CrossRefGoogle Scholar
  6. 6.
    Annunziato A (2008) DNA packaging: nucleosomes and chromatin. Nat Educ 1(1):26Google Scholar
  7. 7.
    Le DD, Fujimori DG (2012) Protein and nucleic acid methylating enzymes: mechanisms and regulation. Curr Opin Chem Biol 16:507–515CrossRefGoogle Scholar
  8. 8.
    Branco MR, Ficz G, Reik W (2011) Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet 13:7–13CrossRefGoogle Scholar
  9. 9.
    Rasmussen KD, Helin K (2016) Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev 30:733–750CrossRefGoogle Scholar
  10. 10.
    Greco CM, Kunderfranco P, Rubino M, Larcher V, Carullo P, Anselmo A et al (2016) DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy. Nat Commun 7:12418CrossRefGoogle Scholar
  11. 11.
    Niu Y, DesMarais TL, Tong Z, Yao Y, Costa M (2015) Oxidative stress alters global histone modification and DNA methylation. Free radical biology & medicine 82:22–28.  https://doi.org/10.1016/j.freeradbiomed.2015.01.028CrossRefGoogle Scholar
  12. 12.
    Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Research 21(3):381–395.  https://doi.org/10.1038/cr.2011.22CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080CrossRefGoogle Scholar
  14. 14.
    Kietzmann T, Petry A, Shvetsova A, Gerhold JM, Gorlach A (2017) The epigenetic landscape related to reactive oxygen species formation in cardiovascular system. Br J Pharmacol 174:1533–1554CrossRefGoogle Scholar
  15. 15.
    Balasubramanian S, Hurley LH, Neidle S (2011) Targeting Gquadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov 10:261–275CrossRefGoogle Scholar
  16. 16.
    Gilsbach R, Preissl S, Grüning BA, Schnick T, Burger L, Benes V, Wurch A, Bonish U, Gunther S, Fleishmann BK, Schubeler D, Hein L (2014) Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease. Nat Commun 5:5288.  https://doi.org/10.1038/ncomms6288CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Thornburg K, Jonker S, O’Tierney P, Chattergoon N, Louey S, Faber J, Giraud G (2011) Regulation of the cardiomyocyte population in the developing heart. Prog Biophys Mol Biol 106(1):289–299.  https://doi.org/10.1016/j.pbiomolbio.2010.11.010CrossRefPubMedGoogle Scholar
  18. 18.
    Han P, Hang CT, Yang J, Chang CP (2011) Chromatin remodelling in cardiac development and physiology. Circ Res 183(3):378–396.  https://doi.org/10.1161/CIRCRESAHA.110.224287CrossRefGoogle Scholar
  19. 19.
    Van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson KA, Kelm RJ Jr, Olson EN (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17(5):662–673.  https://doi.org/10.1016/j.devcel.2009.10.013CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Iruretagoyena JI, Davis W, Bird C, Olsen J, Radue R, Teo Broman A, Kendziorski C, BonDurant SS, Golos T, Bird I, Shah D (2014) Metabolic gene profile in early human fetal heart development. Mol Hum Reprod 20(7):690–700.  https://doi.org/10.1093/molehr/gau026CrossRefPubMedGoogle Scholar
  21. 21.
    Lee S, Choi E, Cha MJ, Hwang KC (2014) Looking into a conceptual framework of ROS-miRNA-atrial fibrillation. Int J Mol Sci 15:21754–21776.  https://doi.org/10.3390/ijms151221754CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hudasek K, Brown ST, Fearon IM (2004) H2O2 regulates recombinant Ca2+ channel alpha1C subunits but does not mediate their sensitivity to acute hypoxia. Biochem Biophys Res Commun 135–141(22):318Google Scholar
  23. 23.
    Morris TE, Sulakhe PV (1997) Sarcoplasmic reticulum Ca2+-pump dysfunction in rat cardiomyocytes briefly exposed to hydroxyl radicals. Free Radic Biol Med 22:37–47CrossRefGoogle Scholar
  24. 24.
    Goldhaber JI (1996) Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes. Am J Physiol 271:H823–H833PubMedGoogle Scholar
  25. 25.
    Zima AV, Blatter LA (2006) Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res 71(2):310–321.  https://doi.org/10.1016/j.cardiores.2006.02.019CrossRefPubMedGoogle Scholar
  26. 26.
    Kyrychenko S, Kyrychenko V, Ma B, Ikeda Y, Sadoshima J, Shirokova N (2015) Pivotal role of miR 448 in the development of ROS-induced cardiomyopathy. Circ Res 108:324–334.  https://doi.org/10.1093/cvr/cvv238CrossRefGoogle Scholar
  27. 27.
    He F, Zuo L (2015) Redox roles of reactive oxygen species in cardiovascular diseases. Int J Mol Sci 16:27770–27780.  https://doi.org/10.3390/ijms161126059CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chaturvedi P, Tyagi SC (2014) Epigenetic mechanisms underlying cardiac degeneration and regeneration. Int J Cardiol 173(1):1–11.  https://doi.org/10.1016/j.ijcard.2014.02.008CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Jain AK, Mehra NK, Swarnakar NK (2015) Role of antioxidants for the treatment of cardiovascular diseases: challenges and oppurtunities. Curr Pharm Des 21(30):4441–4455CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Seema Bhargava
    • 1
  1. 1.Department of Biochemistry, GRIPMERSir Ganga Ram HospitalNew DelhiIndia

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