Molecular Biology Reports

, Volume 42, Issue 4, pp 765–776 | Cite as

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

  • Thomas F. WhayneEmail author


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.


Epigenetics Epigenome Chromatin Flavonoids Histone Methylation Cardiovascular disease prevention 



Abdominal aortic aneurysm




Apoptosis-associated speck-like protein containing a CARD


Caspase recruitment domain


Coronary heart disease




Diabetes mellitus


Deoxyribonucleic acid


Histone deacetylase




Peroxisome proliferator-activated receptor


Peripheral vascular disease


Ribonucleic acid


Reactive oxygen species





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.


  1. 1.
    Jablonka E, Lamb MJ (2002) The changing concept of epigenetics. Ann N Y Acad Sci 981:82–96CrossRefPubMedGoogle Scholar
  2. 2.
    Wilson AG (2008) Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol 79:1514–1519CrossRefPubMedGoogle Scholar
  3. 3.
    Scheen AJ, Junien C (2012) Epigenetics, interface between environment and genes: role in complex diseases. Rev Med Liege 67:250–257PubMedGoogle Scholar
  4. 4.
    Tammen SA, Friso S, Choi SW (2012) Epigenetics: the link between nature and nurture. Mol Aspects Med 34:753–764Google Scholar
  5. 5.
    Fischle W, Wang Y, Allis CD (2003) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183CrossRefPubMedGoogle Scholar
  6. 6.
    Nemeth A, Langst G (2004) Chromatin higher order structure: opening up chromatin for transcription. Brief Funct Genomic Proteomic 2:334–343CrossRefPubMedGoogle Scholar
  7. 7.
    Campos EI, Reinberg D (2009) Histones: annotating chromatin. Annu Rev Genet 43:559–599CrossRefPubMedGoogle Scholar
  8. 8.
    Cheung P, Lau P (2005) Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19:563–573CrossRefPubMedGoogle Scholar
  9. 9.
    Koonin EV, Wolf YI (2009) Is evolution Darwinian or/and Lamarckian? Biol Direct 4:42CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Handel AE, Ramagopalan SV (2010) Is Lamarckian evolution relevant to medicine? BMC Med Genet 11:73CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Jablonka E, Lamb MJ (1989) The inheritance of acquired epigenetic variations. J Theor Biol 139:69–83CrossRefPubMedGoogle Scholar
  12. 12.
    Mathers JC (2008) Session 2: personalised nutrition. Epigenomics: a basis for understanding individual differences? Proc Nutr Soc 67:390–394CrossRefPubMedGoogle Scholar
  13. 13.
    De Rycke M, Liebaers I, Van Steirteghem A (2002) Epigenetic risks related to assisted reproductive technologies: risk analysis and epigenetic inheritance. Hum Reprod 17:2487–2494CrossRefPubMedGoogle Scholar
  14. 14.
    Dupont C, Armant DR, Brenner CA (2009) Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med 27:351–357CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Godfrey KM, Inskip HM, Hanson MA (2011) The long-term effects of prenatal development on growth and metabolism. Semin Reprod Med 29:257–265CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Xu XF, Du LZ (2010) Epigenetics in neonatal diseases. Chin Med J (Engl) 123:2948–2954Google Scholar
  17. 17.
    Levin BE (2008) Epigenetic influences on food intake and physical activity level: review of animal studies. Obesity (Silver Spring) 16(Suppl 3):S51–S54CrossRefGoogle Scholar
  18. 18.
    Bloch W, Suhr F, Zimmer P (2012) Molecular mechanisms of exercise-induced cardiovascular adaptations. Influence of epigenetics, mechanotransduction and free radicals. Herz 37:508–515CrossRefPubMedGoogle Scholar
  19. 19.
    Goh KP, Sum CF (2010) Connecting the dots: molecular and epigenetic mechanisms in type 2 diabetes. Curr Diabetes Rev 6:255–265CrossRefPubMedGoogle Scholar
  20. 20.
    Gilbert ER, Liu D (2012) Epigenetics: the missing link to understanding beta-cell dysfunction in the pathogenesis of type 2 diabetes. Epigenetics 7:841–852CrossRefPubMedCentralPubMedGoogle Scholar
  21. 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 109:1743–1748CrossRefPubMedCentralPubMedGoogle Scholar
  22. 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–e381CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Villeneuve LM, Natarajan R (2011) Epigenetic mechanisms. Contrib Nephrol 170:57–65CrossRefPubMedGoogle Scholar
  24. 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 10:475–486CrossRefPubMedGoogle Scholar
  25. 25.
    Ribaric S (2012) Diet and aging. Oxid Med Cell Longev 2012:741468CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Brewer GJ (2010) Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories. Exp Gerontol 45:173–179CrossRefPubMedCentralPubMedGoogle Scholar
  27. 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 6:1284–1294CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Breitling LP (2013) Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. Arterioscler Thromb Vasc Biol 33:1468–1472CrossRefPubMedGoogle Scholar
  29. 29.
    Ordovas JM, Smith CE (2010) Epigenetics and cardiovascular disease. Nat Rev Cardiol 7:510–519CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Houmard JA, Pories WJ, Dohm GL (2011) Is there a metabolic program in the skeletal muscle of obese individuals? J Obes 2011:250496CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Grun F, Blumberg B (2009) Minireview: the case for obesogens. Mol Endocrinol 23:1127–1134CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Janesick A, Blumberg B (2011) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today 93:34–50CrossRefPubMedGoogle Scholar
  33. 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 153:2823–2830CrossRefPubMedGoogle Scholar
  34. 34.
    Janesick A, Blumberg B (2012) Obesogens, stem cells and the developmental programming of obesity. Int J Androl 35:437–448CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Grun F (2010) Obesogens. Curr Opin Endocrinol Diabetes Obes 17:453–459CrossRefPubMedGoogle Scholar
  36. 36.
    Ruemmele FM, Garnier-Lengline H (2012) Why are genetics important for nutrition? Lessons from epigenetic research. Ann Nutr Metab 60(Suppl 3):38–43CrossRefPubMedGoogle Scholar
  37. 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 13:129–140CrossRefPubMedGoogle Scholar
  38. 38.
    Scheen AJ, Giet D (2012) Role of environment in complex diseases: air pollution and food contaminants. Rev Med Liege 67:226–233PubMedGoogle Scholar
  39. 39.
    Baccarelli A, Ghosh S (2012) Environmental exposures, epigenetics and cardiovascular disease. Curr Opin Clin Nutr Metab Care 15:323–329CrossRefPubMedCentralPubMedGoogle Scholar
  40. 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 179:572–578CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Wrobel K, Caruso JA (2009) Epigenetics: an important challenge for ICP-MS in metallomics studies. Anal Bioanal Chem 393:481–486CrossRefPubMedGoogle Scholar
  42. 42.
    Lund G, Zaina S (2011) Atherosclerosis: an epigenetic balancing act that goes wrong. Curr Atheroscler Rep 13:208–214CrossRefPubMedGoogle Scholar
  43. 43.
    Ordovas JM, Robertson R, Cleirigh EN (2011) Gene-gene and gene-environment interactions defining lipid-related traits. Curr Opin Lipidol 22:129–136CrossRefPubMedGoogle Scholar
  44. 44.
    Ingrosso D, Perna AF (2009) Epigenetics in hyperhomocysteinemic states. A special focus on uremia. Biochim Biophys Acta 1790:892–899CrossRefPubMedGoogle Scholar
  45. 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 354:1578–1588CrossRefPubMedGoogle Scholar
  46. 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) 66:2S19–2S28CrossRefGoogle Scholar
  47. 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–S25CrossRefPubMedGoogle Scholar
  48. 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 103:158–160CrossRefPubMedGoogle Scholar
  49. 49.
    Krishna SM, Dear AE, Norman PE, Golledge J (2010) Genetic and epigenetic mechanisms and their possible role in abdominal aortic aneurysm. Atherosclerosis 212:16–29CrossRefPubMedGoogle Scholar
  50. 50.
    Manolopoulos VG, Ragia G, Tavridou A (2011) Pharmacogenomics of oral antidiabetic medications: current data and pharmacoepigenomic perspective. Pharmacogenomics 12:1161–1191CrossRefPubMedGoogle Scholar
  51. 51.
    Porter KE, Riches K (2013) The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes? Clin Sci (Lond) 125:167–182CrossRefGoogle Scholar
  52. 52.
    Ong TP, Moreno FS, Ross SA (2011) Targeting the epigenome with bioactive food components for cancer prevention. J Nutrigenet Nutrigenomics 4:275–292CrossRefPubMedGoogle Scholar
  53. 53.
    Mai A, Altucci L (2009) Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol 41:199–213CrossRefPubMedGoogle Scholar
  54. 54.
    Dario LS, Rosa MA, Mariela E, Roberto G, Caterina C (2008) Chromatin remodeling agents for cancer therapy. Rev Recent Clin Trials 3:192–203CrossRefPubMedGoogle Scholar
  55. 55.
    Peedicayil J (2006) Epigenetic therapy–a new development in pharmacology. Indian J Med Res 123:17–24PubMedGoogle Scholar
  56. 56.
    Kalebic T (2003) Epigenetic transitions: towards therapeutic targets. Expert Opin Ther Targets 7:693–699CrossRefPubMedGoogle Scholar
  57. 57.
    McKay JA, Mathers JC (2011) Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf) 202:103–118CrossRefGoogle Scholar
  58. 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 2011:265417CrossRefPubMedCentralPubMedGoogle Scholar
  59. 59.
    Duthie SJ (2011) Epigenetic modifications and human pathologies: cancer and CVD. Proc Nutr Soc 70:47–56CrossRefPubMedGoogle Scholar
  60. 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 94:2242–2263CrossRefPubMedGoogle Scholar
  61. 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 68:71–77Google Scholar
  62. 62.
    Milagro FI, Mansego ML, De Miguel C, Martinez JA (2012) Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Aspects Med 34:782–812Google Scholar
  63. 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):4–26CrossRefPubMedGoogle Scholar
  64. 64.
    Haggarty P (2012) Nutrition and the epigenome. Prog Mol Biol Transl Sci 108:427–446CrossRefPubMedGoogle Scholar
  65. 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 23:853–859CrossRefPubMedCentralPubMedGoogle Scholar
  66. 66.
    Oommen AM, Griffin JB, Sarath G, Zempleni J (2005) Roles for nutrients in epigenetic events. J Nutr Biochem 16:74–77CrossRefPubMedGoogle Scholar
  67. 67.
    Hong X, Wang X (2012) Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol 34:655–669CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Burdge GC, Hoile SP, Lillycrop KA (2012) Epigenetics: are there implications for personalised nutrition? Curr Opin Clin Nutr Metab Care 15:442–447CrossRefPubMedGoogle Scholar
  69. 69.
    Rubio-Aliaga I, Kochhar S, Silva-Zolezzi I (2012) Biomarkers of nutrient bioactivity and efficacy: a route toward personalized nutrition. J Clin Gastroenterol 46:545–554CrossRefPubMedGoogle Scholar
  70. 70.
    Capozzi F, Bordoni A (2012) Foodomics: a new comprehensive approach to food and nutrition. Genes Nutr 8:1–4Google Scholar
  71. 71.
    Whayne TF Jr (2011) Vitamin d: popular cardiovascular supplement but benefit must be evaluated. Int J Angiol 20:63–72CrossRefPubMedCentralPubMedGoogle Scholar
  72. 72.
    Hossein-Nezhad A, Holick MF (2012) Optimize dietary intake of vitamin D: an epigenetic perspective. Curr Opin Clin Nutr Metab Care 15:567–579CrossRefPubMedGoogle Scholar
  73. 73.
    Linask KK, Huhta J (2010) Folate protection from congenital heart defects linked with canonical Wnt signaling and epigenetics. Curr Opin Pediatr 22:561–566CrossRefPubMedCentralPubMedGoogle Scholar
  74. 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):3469–3472CrossRefPubMedGoogle Scholar
  75. 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 182:7655–7662CrossRefPubMedGoogle Scholar
  76. 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 29:3207–3210PubMedGoogle Scholar
  77. 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 31:671–675CrossRefPubMedGoogle Scholar
  78. 78.
    McGee SL, Fairlie E, Garnham AP, Hargreaves M (2009) Exercise-induced histone modifications in human skeletal muscle. J Physiol 587:5951–5958CrossRefPubMedCentralPubMedGoogle Scholar
  79. 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 18:1208–1246Google Scholar
  80. 80.
    Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887CrossRefPubMedGoogle Scholar
  81. 81.
    Fujita J (2013) Report of the American Heart Association (AHA) scientific sessions 2012, Los Angeles. Circ J 77:35–40CrossRefPubMedGoogle Scholar
  82. 82.
    Sun X, Fu X, Han W, Zhao Y, Liu H (2010) Can controlled cellular reprogramming be achieved using microRNAs? Ageing Res Rev 9:475–483CrossRefPubMedGoogle Scholar
  83. 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 4:14CrossRefPubMedCentralPubMedGoogle Scholar
  84. 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 378:1997–2004CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Division of Cardiovascular Medicine, Gill Heart InstituteUniversity of KentuckyLexingtonUSA

Personalised recommendations