Skip to main content

Epigenetics in the development, modification, and prevention of cardiovascular disease

Abstract

Epigenetics has major relevance to all disease processes; cardiovascular (CV) disease and its related conditions are no exception. Epigenetics is defined as the study of heritable alterations in gene expression, or cellular phenotype, and goes far beyond a pure genetic approach. A more precise definition is that epigenetics represents all the meiotically and mitotically inherited changes in gene expression that are not encoded on the deoxyribonucleic acid (DNA) sequence itself. Major epigenetic mechanisms are modifications of histone proteins in chromatin and DNA methylation (which does not alter the DNA sequence). There is increasing evidence for the involvement of epigenetics in human disease such as cancer, inflammatory disease and CV disease. Other chronic diseases are also susceptible to epigenetic modification such as metabolic diseases including obesity, metabolic syndrome, and diabetes mellitus. There is much evidence for the modification of epigenetics by nutrition and exercise. Through these modifications, there is infinite potential for benefit for the fetus, the newborn, and the individual as well as population effects. Association with CV disease, including coronary heart disease and peripheral vascular disease, is evident through epigenetic relationships and modification by major CV risk factors such as tobacco abuse. Aging itself may be altered by epigenetic modification. Knowledge of epigenetics and its relevance to the development, modification, and prevention of CV disease is in a very preliminary stage but has an infinite future.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

AAA:

Abdominal aortic aneurysm

AdoHcy:

S-adenosylhomocysteine

ASC:

Apoptosis-associated speck-like protein containing a CARD

CARD:

Caspase recruitment domain

CHD:

Coronary heart disease

CV:

Cardiovascular

DM:

Diabetes mellitus

DNA:

Deoxyribonucleic acid

HDAC:

Histone deacetylase

PAR:

Poly(ADP-ribosylation)

PPAR:

Peroxisome proliferator-activated receptor

PVD:

Peripheral vascular disease

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

SAM:

S-adenosylmethionine

References

  1. Jablonka E, Lamb MJ (2002) The changing concept of epigenetics. Ann N Y Acad Sci 981:82–96

    Article  PubMed  Google Scholar 

  2. Wilson AG (2008) Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol 79:1514–1519

    Article  CAS  PubMed  Google Scholar 

  3. Scheen AJ, Junien C (2012) Epigenetics, interface between environment and genes: role in complex diseases. Rev Med Liege 67:250–257

    CAS  PubMed  Google Scholar 

  4. Tammen SA, Friso S, Choi SW (2012) Epigenetics: the link between nature and nurture. Mol Aspects Med 34:753–764

  5. Fischle W, Wang Y, Allis CD (2003) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183

    Article  CAS  PubMed  Google Scholar 

  6. Nemeth A, Langst G (2004) Chromatin higher order structure: opening up chromatin for transcription. Brief Funct Genomic Proteomic 2:334–343

    Article  CAS  PubMed  Google Scholar 

  7. Campos EI, Reinberg D (2009) Histones: annotating chromatin. Annu Rev Genet 43:559–599

    Article  CAS  PubMed  Google Scholar 

  8. Cheung P, Lau P (2005) Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19:563–573

    Article  CAS  PubMed  Google Scholar 

  9. Koonin EV, Wolf YI (2009) Is evolution Darwinian or/and Lamarckian? Biol Direct 4:42

    Article  PubMed Central  PubMed  Google Scholar 

  10. Handel AE, Ramagopalan SV (2010) Is Lamarckian evolution relevant to medicine? BMC Med Genet 11:73

    Article  PubMed Central  PubMed  Google Scholar 

  11. Jablonka E, Lamb MJ (1989) The inheritance of acquired epigenetic variations. J Theor Biol 139:69–83

    Article  CAS  PubMed  Google Scholar 

  12. Mathers JC (2008) Session 2: personalised nutrition. Epigenomics: a basis for understanding individual differences? Proc Nutr Soc 67:390–394

    Article  PubMed  Google Scholar 

  13. De Rycke M, Liebaers I, Van Steirteghem A (2002) Epigenetic risks related to assisted reproductive technologies: risk analysis and epigenetic inheritance. Hum Reprod 17:2487–2494

    Article  PubMed  Google Scholar 

  14. Dupont C, Armant DR, Brenner CA (2009) Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med 27:351–357

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Godfrey KM, Inskip HM, Hanson MA (2011) The long-term effects of prenatal development on growth and metabolism. Semin Reprod Med 29:257–265

    Article  PubMed Central  PubMed  Google Scholar 

  16. Xu XF, Du LZ (2010) Epigenetics in neonatal diseases. Chin Med J (Engl) 123:2948–2954

    CAS  Google Scholar 

  17. Levin BE (2008) Epigenetic influences on food intake and physical activity level: review of animal studies. Obesity (Silver Spring) 16(Suppl 3):S51–S54

    Article  Google Scholar 

  18. Bloch W, Suhr F, Zimmer P (2012) Molecular mechanisms of exercise-induced cardiovascular adaptations. Influence of epigenetics, mechanotransduction and free radicals. Herz 37:508–515

    Article  CAS  PubMed  Google Scholar 

  19. Goh KP, Sum CF (2010) Connecting the dots: molecular and epigenetic mechanisms in type 2 diabetes. Curr Diabetes Rev 6:255–265

    Article  CAS  PubMed  Google Scholar 

  20. Gilbert ER, Liu D (2012) Epigenetics: the missing link to understanding beta-cell dysfunction in the pathogenesis of type 2 diabetes. Epigenetics 7:841–852

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A 109:1743–1748

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Ahmad S, Heraclides A, Sun Q, Elgzyri T, Ronn T, Ling C, Isomaa B, Eriksson KF, Groop L, Franks PW, Hansson O (2012) Telomere length in blood and skeletal muscle in relation to measures of glycaemia and insulinaemia. Diabet Med 29:e377–e381

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Villeneuve LM, Natarajan R (2011) Epigenetic mechanisms. Contrib Nephrol 170:57–65

    Article  CAS  PubMed  Google Scholar 

  24. Kaliman P, Parrizas M, Lalanza JF, Camins A, Escorihuela RM, Pallas M (2011) Neurophysiological and epigenetic effects of physical exercise on the aging process. Ageing Res Rev 10:475–486

    Article  PubMed  Google Scholar 

  25. Ribaric S (2012) Diet and aging. Oxid Med Cell Longev 2012:741468

    Article  PubMed Central  PubMed  Google Scholar 

  26. Brewer GJ (2010) Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories. Exp Gerontol 45:173–179

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Suter M, Ma J, Harris A, Patterson L, Brown KA, Shope C, Showalter L, Abramovici A, Aagaard-Tillery KM (2011) Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression. Epigenetics 6:1284–1294

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Breitling LP (2013) Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. Arterioscler Thromb Vasc Biol 33:1468–1472

    Article  CAS  PubMed  Google Scholar 

  29. Ordovas JM, Smith CE (2010) Epigenetics and cardiovascular disease. Nat Rev Cardiol 7:510–519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Houmard JA, Pories WJ, Dohm GL (2011) Is there a metabolic program in the skeletal muscle of obese individuals? J Obes 2011:250496

    Article  PubMed Central  PubMed  Google Scholar 

  31. Grun F, Blumberg B (2009) Minireview: the case for obesogens. Mol Endocrinol 23:1127–1134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Janesick A, Blumberg B (2011) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today 93:34–50

    Article  CAS  PubMed  Google Scholar 

  33. Masuyama H, Hiramatsu Y (2012) Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology 153:2823–2830

    Article  CAS  PubMed  Google Scholar 

  34. Janesick A, Blumberg B (2012) Obesogens, stem cells and the developmental programming of obesity. Int J Androl 35:437–448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Grun F (2010) Obesogens. Curr Opin Endocrinol Diabetes Obes 17:453–459

    Article  PubMed  Google Scholar 

  36. Ruemmele FM, Garnier-Lengline H (2012) Why are genetics important for nutrition? Lessons from epigenetic research. Ann Nutr Metab 60(Suppl 3):38–43

    Article  CAS  PubMed  Google Scholar 

  37. Roth CL, Sathyanarayana S (2012) Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA). Rev Endocr Metab Disord 13:129–140

    Article  PubMed  Google Scholar 

  38. Scheen AJ, Giet D (2012) Role of environment in complex diseases: air pollution and food contaminants. Rev Med Liege 67:226–233

    CAS  PubMed  Google Scholar 

  39. Baccarelli A, Ghosh S (2012) Environmental exposures, epigenetics and cardiovascular disease. Curr Opin Clin Nutr Metab Care 15:323–329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179:572–578

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Wrobel K, Caruso JA (2009) Epigenetics: an important challenge for ICP-MS in metallomics studies. Anal Bioanal Chem 393:481–486

    Article  CAS  PubMed  Google Scholar 

  42. Lund G, Zaina S (2011) Atherosclerosis: an epigenetic balancing act that goes wrong. Curr Atheroscler Rep 13:208–214

    Article  CAS  PubMed  Google Scholar 

  43. Ordovas JM, Robertson R, Cleirigh EN (2011) Gene-gene and gene-environment interactions defining lipid-related traits. Curr Opin Lipidol 22:129–136

    Article  CAS  PubMed  Google Scholar 

  44. Ingrosso D, Perna AF (2009) Epigenetics in hyperhomocysteinemic states. A special focus on uremia. Biochim Biophys Acta 1790:892–899

    Article  CAS  PubMed  Google Scholar 

  45. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588

    Article  CAS  PubMed  Google Scholar 

  46. Junien C, Gallou-Kabani C, Vige A, Gross MS (2005) [Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations]. Ann Endocrinol (Paris) 66:2S19–2S28

    Article  CAS  Google Scholar 

  47. Hanley B, Dijane J, Fewtrell M, Grynberg A, Hummel S, Junien C, Koletzko B, Lewis S, Renz H, Symonds M, Gros M, Harthoorn L, Mace K, Samuels F, van Der Beek EM (2010) Metabolic imprinting, programming and epigenetics–a review of present priorities and future opportunities. Br J Nutr 104(Suppl 1):S1–S25

    Article  CAS  PubMed  Google Scholar 

  48. Sukhija R, Aronow WS, Yalamanchili K, Peterson SJ, Frishman WH, Babu S (2005) Association of ankle-brachial index with severity of angiographic coronary artery disease in patients with peripheral arterial disease and coronary artery disease. Cardiology 103:158–160

    Article  CAS  PubMed  Google Scholar 

  49. Krishna SM, Dear AE, Norman PE, Golledge J (2010) Genetic and epigenetic mechanisms and their possible role in abdominal aortic aneurysm. Atherosclerosis 212:16–29

    Article  CAS  PubMed  Google Scholar 

  50. Manolopoulos VG, Ragia G, Tavridou A (2011) Pharmacogenomics of oral antidiabetic medications: current data and pharmacoepigenomic perspective. Pharmacogenomics 12:1161–1191

    Article  CAS  PubMed  Google Scholar 

  51. Porter KE, Riches K (2013) The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes? Clin Sci (Lond) 125:167–182

    Article  CAS  Google Scholar 

  52. Ong TP, Moreno FS, Ross SA (2011) Targeting the epigenome with bioactive food components for cancer prevention. J Nutrigenet Nutrigenomics 4:275–292

    Article  CAS  PubMed  Google Scholar 

  53. Mai A, Altucci L (2009) Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol 41:199–213

    Article  CAS  PubMed  Google Scholar 

  54. Dario LS, Rosa MA, Mariela E, Roberto G, Caterina C (2008) Chromatin remodeling agents for cancer therapy. Rev Recent Clin Trials 3:192–203

    Article  CAS  PubMed  Google Scholar 

  55. Peedicayil J (2006) Epigenetic therapy–a new development in pharmacology. Indian J Med Res 123:17–24

    CAS  PubMed  Google Scholar 

  56. Kalebic T (2003) Epigenetic transitions: towards therapeutic targets. Expert Opin Ther Targets 7:693–699

    Article  CAS  PubMed  Google Scholar 

  57. McKay JA, Mathers JC (2011) Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf) 202:103–118

    Article  CAS  Google Scholar 

  58. Wheatley KE, Nogueira LM, Perkins SN, Hursting SD (2011) Differential effects of calorie restriction and exercise on the adipose transcriptome in diet-induced obese mice. J Obes 2011:265417

    Article  PubMed Central  PubMed  Google Scholar 

  59. Duthie SJ (2011) Epigenetic modifications and human pathologies: cancer and CVD. Proc Nutr Soc 70:47–56

    Article  CAS  PubMed  Google Scholar 

  60. Jimenez-Chillaron JC, Diaz R, Martinez D, Pentinat T, Ramon-Krauel M, Ribo S, Plosch T (2012) The role of nutrition on epigenetic modifications and their implications on health. Biochimie 94:2242–2263

    Article  CAS  PubMed  Google Scholar 

  61. Symonds ME (2009) Conference on “Multidisciplinary approaches to nutritional problems”. Symposium on “Diabetes and health”. Nutrition and its contribution to obesity and diabetes: a life-course approach to disease prevention? Proc Nutr Soc 68:71–77

  62. Milagro FI, Mansego ML, De Miguel C, Martinez JA (2012) Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Aspects Med 34:782–812

  63. Wu G, Imhoff-Kunsch B, Girard AW (2012) Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr Perinat Epidemiol 26(Suppl 1):4–26

    Article  PubMed  Google Scholar 

  64. Haggarty P (2012) Nutrition and the epigenome. Prog Mol Biol Transl Sci 108:427–446

    Article  CAS  PubMed  Google Scholar 

  65. Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23:853–859

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Oommen AM, Griffin JB, Sarath G, Zempleni J (2005) Roles for nutrients in epigenetic events. J Nutr Biochem 16:74–77

    Article  CAS  PubMed  Google Scholar 

  67. Hong X, Wang X (2012) Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol 34:655–669

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Burdge GC, Hoile SP, Lillycrop KA (2012) Epigenetics: are there implications for personalised nutrition? Curr Opin Clin Nutr Metab Care 15:442–447

    Article  CAS  PubMed  Google Scholar 

  69. Rubio-Aliaga I, Kochhar S, Silva-Zolezzi I (2012) Biomarkers of nutrient bioactivity and efficacy: a route toward personalized nutrition. J Clin Gastroenterol 46:545–554

    Article  CAS  PubMed  Google Scholar 

  70. Capozzi F, Bordoni A (2012) Foodomics: a new comprehensive approach to food and nutrition. Genes Nutr 8:1–4

  71. Whayne TF Jr (2011) Vitamin d: popular cardiovascular supplement but benefit must be evaluated. Int J Angiol 20:63–72

    Article  PubMed Central  PubMed  Google Scholar 

  72. Hossein-Nezhad A, Holick MF (2012) Optimize dietary intake of vitamin D: an epigenetic perspective. Curr Opin Clin Nutr Metab Care 15:567–579

    Article  CAS  PubMed  Google Scholar 

  73. Linask KK, Huhta J (2010) Folate protection from congenital heart defects linked with canonical Wnt signaling and epigenetics. Curr Opin Pediatr 22:561–566

    Article  PubMed Central  PubMed  Google Scholar 

  74. Sanchis-Gomar F, Garcia-Gimenez JL, Perez-Quilis C, Gomez-Cabrera MC, Pallardo FV, Lippi G (2012) Physical exercise as an epigenetic modulator. Eustress, the “positive stress” as an effector of gene expression. J Strength Cond Res 26(12):3469–3472

    Article  PubMed  Google Scholar 

  75. Hasegawa M, Imamura R, Motani K, Nishiuchi T, Matsumoto N, Kinoshita T, Suda T (2009) Mechanism and repertoire of ASC-mediated gene expression. J Immunol 182:7655–7662

    Article  CAS  PubMed  Google Scholar 

  76. Gordian E, Ramachandran K, Singal R (2009) Methylation mediated silencing of TMS1 in breast cancer and its potential contribution to docetaxel cytotoxicity. Anticancer Res 29:3207–3210

    CAS  PubMed  Google Scholar 

  77. Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, Higuchi K, Itano N, Shiohara M, Oh T, Taniguchi S (2010) Exercise effects on methylation of ASC gene. Int J Sports Med 31:671–675

    Article  CAS  PubMed  Google Scholar 

  78. McGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587:5951–5958

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M (2012) Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid Redox Signal 18:1208–1246

  80. Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887

    Article  CAS  PubMed  Google Scholar 

  81. Fujita J (2013) Report of the American Heart Association (AHA) scientific sessions 2012, Los Angeles. Circ J 77:35–40

    Article  PubMed  Google Scholar 

  82. Sun X, Fu X, Han W, Zhao Y, Liu H (2010) Can controlled cellular reprogramming be achieved using microRNAs? Ageing Res Rev 9:475–483

    Article  CAS  PubMed  Google Scholar 

  83. Thomas BJ, Rubio ED, Krumm N, Broin PO, Bomsztyk K, Welcsh P, Greally JM, Golden AA, Krumm A (2011) Allele-specific transcriptional elongation regulates monoallelic expression of the IGF2BP1 gene. Epigenetics Chromatin 4:14

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Jungebluth P, Alici E, Baiguera S, Le Blanc K, Blomberg P, Bozoky B, Crowley C, Einarsson O, Grinnemo KH, Gudbjartsson T, Le Guyader S, Henriksson G, Hermanson O, Juto JE, Leidner B, Lilja T, Liska J, Luedde T, Lundin V, Moll G, Nilsson B, Roderburg C, Stromblad S, Sutlu T, Teixeira AI, Watz E, Seifalian A, Macchiarini P (2011) Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 378:1997–2004

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author wishes to recognize the excellent editorial critique of Susan Quick and its contribution to this article.

Conflict of interest

The author has no conflicts of interest to declare with any pharmaceutical or medical device company. Also, he has no stock ownership or other ownership conflict to report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas F. Whayne.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Whayne, T.F. Epigenetics in the development, modification, and prevention of cardiovascular disease. Mol Biol Rep 42, 765–776 (2015). https://doi.org/10.1007/s11033-014-3727-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3727-z

Keywords

  • Epigenetics
  • Epigenome
  • Chromatin
  • Flavonoids
  • Histone
  • Methylation
  • Cardiovascular disease prevention