Skip to main content

Epigenetics in Cardiovascular Regulation

  • Chapter
  • First Online:
Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

Epidemiological studies have shown an association between pathologic events occurring during early life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called fetal programming of adult disease hypothesis. In line with this hypothesis, short-term exposure to hypoxia after birth predisposes to exaggerated hypoxic pulmonary vasoconstriction later in life in rats, and transient perinatal hypoxia predisposes to exaggerated pulmonary hypertension during short-term exposure to high altitude in humans. Along the same lines, in recent studies in Bolivian high-altitude dwellers, we found that preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction possibly related to impaired NO bioavailability and augmented oxidative stress. Very recent data from our lab suggest that assisted reproductive technologies may represent another important example consistent with this hypothesis. The mechanisms underpinning the developmental origin of this vascular dysfunction are poorly understood. Increasing evidence suggests that epigenetic alterations, such as DNA methylation or histone acetylation may play a role.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Barker DJ. Fetal origins of cardiovascular disease. Ann Med. 1999;31 Suppl 1:3–6.

    PubMed  Google Scholar 

  2. Barker DJ. The fetal and infant origins of disease. Eur J Clin Invest. 1995;25:457–63.

    Article  CAS  PubMed  Google Scholar 

  3. Berger MM, Hesse C, Dehnert C, Siedler H, Kleinbongard P, Bardenheuer HJ, Kelm M, Bartsch P, Haefeli WE. Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema. Am J Respir Crit Care Med. 2005;172:763–7.

    Article  PubMed  Google Scholar 

  4. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA. Dietary protein restriction of pregnant rats in the f0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the f1 and f2 generations. Br J Nutr. 2007;97:435–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part i. Circulation. 2003;108:1527–32.

    Article  PubMed  Google Scholar 

  6. Franco MC, Akamine EH, Reboucas N, Carvalho MH, Tostes RC, Nigro D, Fortes ZB. Long-term effects of intrauterine malnutrition on vascular function in female offspring: implications of oxidative stress. Life Sci. 2007;80:709–15.

    Article  CAS  PubMed  Google Scholar 

  7. Friedman AH, Fahey JT. The transition from fetal to neonatal circulation: normal responses and implications for infants with heart disease. Semin Perinatol. 1993;17:106–21.

    CAS  PubMed  Google Scholar 

  8. Gemignani V, Bianchini E, Faita F, Giannarelli C, Plantinga Y, Ghiadoni L, Demi M. Ultrasound measurement of the brachial artery flow-mediated dilation without ecg gating. Ultrasound Med Biol. 2008;34:385–91.

    Article  PubMed  Google Scholar 

  9. Gluckman PD, Hanson MA, Beedle AS. Non-genomic transgenerational inheritance of disease risk. Bioessays. 2007;29:145–54.

    Article  CAS  PubMed  Google Scholar 

  10. Godfrey KM. The role of the placenta in fetal programming—a review. Placenta. 2002;23(Suppl A):S20–7.

    Article  PubMed  Google Scholar 

  11. Hakim TS, Mortola JP. Pulmonary vascular resistance in adult rats exposed to hypoxia in the neonatal period. Can J Physiol Pharmacol. 1990;68:419–24.

    Article  CAS  PubMed  Google Scholar 

  12. Hampl V, Herget J. Perinatal hypoxia increases hypoxic pulmonary vasoconstriction in adults rats recovering from chronic exposure to hypoxia. Am Rev Respir Dis. 1990;142:619–24.

    Article  CAS  PubMed  Google Scholar 

  13. Ingelfinger JR. Pathogenesis of perinatal programming. Curr Opin Nephrol Hypertens. 2004;13:459–64.

    Article  CAS  PubMed  Google Scholar 

  14. Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, Lehtimaki T, Ronnemaa T, Viikari J, Raitakari OT. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109:1750–5.

    Article  PubMed  Google Scholar 

  15. Jayet PY, Rimoldi SF, Stuber T, Salmon CS, Hutter D, Rexhaj E, Thalmann S, Schwab M, Turini P, Sartori-Cucchia C, Nicod P, Villena M, Allemann Y, Scherrer U, Sartori C. Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation. 2010;122:488–94.

    Article  PubMed  Google Scholar 

  16. Kajantie E, Eriksson JG, Osmond C, Thornburg K, Barker DJ. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 2009;40:1176–80.

    Article  PubMed  Google Scholar 

  17. Langley-Evans SC. Developmental programming of health and disease. Proc Nutr Soc. 2006;65:97–105.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Niemitz EL, Feinberg AP. Epigenetics and assisted reproductive technology: a call for investigation. Am J Hum Genet. 2004;74:599–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rexhaj E, Bloch J, Jayet PY, Rimoldi SF, Dessen P, Mathieu C, Tolsa JF, Nicod P, Scherrer U, Sartori C. Fetal programming of vascular dysfunction in mice: role of epigenetic mechanisms. Am J Physiol Heart Circ Physiol. 2011;301:H247–52.

    Article  CAS  PubMed  Google Scholar 

  20. Sartori C, Allemann Y, Trueb L, Delabays A, Nicod P, Scherrer U. Augmented vasoreactivity in adult life associated with perinatal vascular insult. Lancet. 1999;353:2205–7.

    Article  CAS  PubMed  Google Scholar 

  21. Sartori C, Rimoldi SF, Scherrer U. Lung fluid movements in hypoxia. Prog Cardiovasc Dis. 2010;52:493–9.

    Google Scholar 

  22. Scherrer U, Allemann Y, Jayet PY, Rexhaj E, Sartori C. High altitude, a natural research laboratory for the study of cardiovascular physiology and pathophysiology. Prog Cardiovasc Dis. 2010;52:451–5.

    Google Scholar 

  23. Scherrer U, Sartori C, Lepori M, Allemann Y, Duplain H, Trueb L, Nicod P. High-altitude pulmonary edema: from exaggerated pulmonary hypertension to a defect in transepithelial sodium transport. Adv Exp Med Biol. 1999;474:93–107.

    Article  CAS  PubMed  Google Scholar 

  24. Seidman DS, Laor A, Gale R, Stevenson DK, Mashiach S, Danon YL. Pre-eclampsia and offspring’s blood pressure, cognitive ability and physical development at 17-years-of-age. Br J Obstet Gynaecol. 1991;98:1009–14.

    Article  CAS  PubMed  Google Scholar 

  25. Sutcliffe AG, Ludwig M. Outcome of assisted reproduction. Lancet. 2007;370:351–9.

    Article  PubMed  Google Scholar 

  26. Szyf M, Weaver IC, Champagne FA, Diorio J, Meaney MJ. Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat. Front Neuroendocrinol. 2005;26:139–62.

    Article  CAS  PubMed  Google Scholar 

  27. Vatten LJ, Romundstad PR, Holmen TL, Hsieh CC, Trichopoulos D, Stuver SO. Intrauterine exposure to preeclampsia and adolescent blood pressure, body size, and age at menarche in female offspring. Obstet Gynecol. 2003;101:529–33.

    PubMed  Google Scholar 

  28. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7:847–54.

    Article  CAS  PubMed  Google Scholar 

  29. Weaver IC, Meaney MJ, Szyf M. Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci U S A. 2006;103:3480–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Weitzman SA, Turk PW, Milkowski DH, Kozlowski K. Free radical adducts induce alterations in DNA cytosine methylation. Proc Natl Acad Sci U S A. 1994;91:1261–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Whitelaw NC, Whitelaw E. Transgenerational epigenetic inheritance in health and disease. Curr Opin Genet Dev. 2008;18:273–9.

    Article  CAS  PubMed  Google Scholar 

  32. Ying M, Xu R, Wu X, Zhu H, Zhuang Y, Han M, Xu T. Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for drpla. J Biol Chem. 2006;281:12580–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudio Sartori .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Sartori, C., Rimoldi, S.F., Rexhaj, E., Allemann, Y., Scherrer, U. (2016). Epigenetics in Cardiovascular Regulation. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_4

Download citation

Publish with us

Policies and ethics