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The programming of cardiovascular disease

Part of: Sir David Barker Symposium

Published online by Cambridge University Press:  15 July 2015

K. L. Thornburg
K. L. Thornburg*
Affiliation:
Oregon Health & Science University, Heart Research Center, Portland, OR, USA
*
* Address of correspondence: K. L. Thornburg, Center for Developmental Health, Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, 3303 SW Bond Avenue, OR 97239, Portland.(Email [email protected])
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Abstract

In spite of improving life expectancy over the course of the previous century, the health of the U.S. population is now worsening. Recent increasing rates of type 2 diabetes, obesity and uncontrolled high blood pressure predict a growing incidence of cardiovascular disease and shortened average lifespan. The daily >$1billion current price tag for cardiovascular disease in the United States is expected to double within the next decade or two. Other countries are seeing similar trends. Current popular explanations for these trends are inadequate. Rather, increasingly poor diets in young people and in women during pregnancy are a likely cause of declining health in the U.S. population through a process known as programming. The fetal cardiovascular system is sensitive to poor maternal nutritional conditions during the periconceptional period, in the womb and in early postnatal life. Developmental plasticity accommodates changes in organ systems that lead to endothelial dysfunction, small coronary arteries, stiffer vascular tree, fewer nephrons, fewer cardiomyocytes, coagulopathies and atherogenic blood lipid profiles in fetuses born at the extremes of birthweight. Of equal importance are epigenetic modifications to genes driving important growth regulatory processes. Changes in microRNA, DNA methylation patterns and histone structure have all been implicated in the cardiovascular disease vulnerabilities that cross-generations. Recent experiments offer hope that detrimental epigenetic changes can be prevented or reversed. The large number of studies that provide the foundational concepts for the developmental origins of disease can be traced to the brilliant discoveries of David J.P. Barker.

Keywords

epigeneticsfetal programmingheart diseaseroots of cardiovascular diseaseworsening health
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 5: Themed Issue: David Barker commemorative meeting, September 2014; Prenatal Exposures and Health Outcomes , October 2015 , pp. 366 - 376
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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References

1. Chobanian, AV. Shattuck Lecture. The hypertension paradox – more uncontrolled disease despite improved therapy. N Engl J Med. 2009; 361, 878–887.Google Scholar
2. Wang, TJ, Vasan, RS. Epidemiology of uncontrolled hypertension in the United States. Circulation. 2005; 112, 1651–1662.Google Scholar
3. Sarafidis, PA, Georgianos, P, Bakris, GL. Resistant hypertension – its identification and epidemiology. Nat Rev Nephrol. 2013; 9, 51–58.Google Scholar
4. Eckel, RH, Krauss, RM. American Heart Association call to action: obesity as a major risk factor for coronary heart disease. AHA Nutrition Committee. Circulation. 1998; 97, 2099–2100.Google Scholar
5. Grundy, SM, Benjamin, IJ, Burke, GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999; 100, 1134–1146.Google Scholar
6. Rosendorff, C, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007; 115, 2761–2788.Google Scholar
7. Go, AS, et al. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation. 2014; 129, e28–e292.Google Scholar
8. Gross, LS, et al. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr. 2004; 79, 774–779.Google Scholar
9. Lyon, HN, Hirschhorn, JN. Genetics of common forms of obesity: a brief overview. Am J Clin Nutr. 2005; 82, 215S–217S.Google Scholar
10. Rodriguez-Ventura, AL, et al. Barriers to lose weight from the perspective of children with overweight/obesity and their parents: a sociocultural approach. J Obes. 2014; 2014, 575184.CrossRefGoogle ScholarPubMed
11. Herman, KM, et al. Combined physical activity/sedentary behaviour associations with indices of adiposity in 8 to 10 year old children. J Phys Act Health. 2015; 12, 20–29.Google Scholar
12. Teo, K, et al. Prevalence of a healthy lifestyle among individuals with cardiovascular disease in high-, middle- and low-income countries: The Prospective Urban Rural Epidemiology (PURE) study. JAMA. 2013; 309, 1613–1621.CrossRefGoogle ScholarPubMed
13. Talmud, PJ, Cooper, JA, Morris, RW, et al. Sixty-five common genetic variants and prediction of type 2 diabetes. Diabetes. 2015; 64, 1830–1840.Google Scholar
14. Barker, DJ, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564–567.Google Scholar
15. Barker, DJ, Osmond, C, Law, CM. The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. J Epidemiol Community Health. 1989; 43, 237–240.Google Scholar
16. Barker, DJ, et al. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577–580.Google Scholar
17. Smith, LP, et al. Trends in US home food preparation and consumption: analysis of national nutrition surveys and time use studies from 1965–1966 to 2007–2008. Nutr J. 2013; 12, 45–55.Google Scholar
18. Syddall, HE, et al. Cohort profile: the Hertfordshire cohort study. Int J Epidemiol. 2005; 34, 1234–1242.Google Scholar
19. Andersen, LG, et al. Birth weight, childhood body mass index and risk of coronary heart disease in adults: combined historical cohort studies. PLoS One. 2010; 5, e14126.Google Scholar
20. Barker, DJ, et al. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002; 31, 1235–1239.Google Scholar
21. Leon, DA, et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29. BMJ. 1998; 317, 241–245.Google Scholar
22. Fan, Z, et al. Relationship between birth size and coronary heart disease in China. Ann Med. 2010; 42, 596–602.Google Scholar
23. Stein, CE, et al. Fetal growth and coronary heart disease in south India. Lancet. 1996; 348, 1269–1273.Google Scholar
24. Rich-Edwards, JW, et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ. 1997; 315, 396–400.Google Scholar
25. Eriksson, JG, et al. Mother’s body size and placental size predict coronary heart disease in men. Eur Heart J. 2011; 32, 2297–2303.Google Scholar
26. Barker, DJ, et al. The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood. Eur J Heart Fail. 2010; 12, 819–825.Google Scholar
27. Barker, DJ, et al. The placental origins of sudden cardiac death. Int J Epidemiol. 2012; 41, 1394–1399.Google Scholar
28. Martyn, CN, Barker, DJ, Osmond, C. Mothers’ pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet. 1996; 348, 1264–1268.Google Scholar
29. Langley-Evans, SC, Phillips, GJ, Jackson, AA. In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr. 1994; 13, 319–324.Google Scholar
30. Barker, DJ, Thornburg, KL. The obstetric origins of health for a lifetime. Clin Obstet Gynecol. 2013; 56, 511–519.Google Scholar
31. Aiken, CE, Ozanne, SE. Transgenerational developmental programming. Hum Reprod Update. 2014; 20, 63–75.Google Scholar
32. Fleming, TP, et al. Nutrition of females during the peri-conceptional period and effects on foetal programming and health of offspring. Anim Reprod Sci. 2012; 130, 193–197.Google Scholar
33. Watkins, AJ, Lucas, ES, Fleming, TP. Impact of the periconceptional environment on the programming of adult disease. J Dev Orig Health Dis. 2010; 1, 87–95.Google Scholar
34. Watkins, AJ, et al. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J Physiol. 2008; 586, 2231–2244.CrossRefGoogle ScholarPubMed
35. Watkins, AJ, et al. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS One. 2011; 6, e28745.Google Scholar
36. Kwong, WY, et al. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127, 4195–4202.Google Scholar
37. Valenzuela-Alcaraz, B, et al. Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally. Circulation. 2013; 128, 1442–1450.Google Scholar
38. Scherrer, U, et al. Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies. Circulation. 2012; 125, 1890–1896.Google Scholar
39. Eskild, A, Monkerud, L, Tanbo, T. Birthweight and placental weight; do changes in culture media used for IVF matter? Comparisons with spontaneous pregnancies in the corresponding time periods. Hum Reprod. 2013; 28, 3207–3214.Google Scholar
40. Kleijkers, SH, et al. IVF culture medium affects post-natal weight in humans during the first 2 years of life. Hum Reprod. 2014; 29, 661–669.Google Scholar
41. Padhee, M, et al. The periconceptional environment and cardiovascular disease: does in vitro embryo culture and transfer influence cardiovascular development and health? Nutrients. 2015; 7, 1378–1425.Google Scholar
42. Thornburg, KL, O’Tierney, PF, Louey, S. Review: the placenta is a programming agent for cardiovascular disease. Placenta. 2010; 31, S54–S59.Google Scholar
43. Godfrey, KM. The role of the placenta in fetal programming – a review. Placenta. 2002; 23, S20–S27.Google Scholar
44. Barker, DJ, et al. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990; 301, 259–262.Google Scholar
45. Barker, DJ, et al. The surface area of the placenta and hypertension in the offspring in later life. Int J Dev Biol. 2010; 54, 525–530.Google Scholar
46. van Abeelen, AF, et al. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta. 2011; 32, 694–698.Google Scholar
47. Roseboom, TJ, et al. Effects of famine on placental size and efficiency. Placenta. 2011; 32, 395–399.Google Scholar
48. Alwasel, SH, et al. Changes in placental size during Ramadan. Placenta. 2010; 31, 607–610.Google Scholar
49. Alwasel, SH, et al. The breadth of the placental surface but not the length is associated with body size at birth. Placenta. 2012; 33, 619–622.Google Scholar
50. Alwasel, SH, et al. Intergenerational effects of in utero exposure to Ramadan in Tunisia. Am J Hum Biol. 2013; 25, 341–343.Google Scholar
51. Alwasel, SH, et al. The velocity of fetal growth is associated with the breadth of the placental surface, but not with the length. Am J Hum Biol. 2013; 25, 534–537.Google Scholar
52. Alwasel, SH, et al. Sex differences in regional specialisation across the placental surface. Placenta. 2014; 35, 365–369.Google Scholar
53. Winder, NR, et al. Mother’s lifetime nutrition and the size, shape and efficiency of the placenta. Placenta. 2011; 32, 806–810.Google Scholar
54. Andersen, TA, Troelsen Kde, L, Larsen, LA. Of mice and men: molecular genetics of congenital heart disease. Cell Mol Life Sci. 2014; 71, 1327–1352.Google Scholar
55. Richards, AA, Garg, V. Genetics of congenital heart disease. Curr Cardiol Rev. 2010; 6, 91–97.Google Scholar
56. Wolf, M, Basson, CT. The molecular genetics of congenital heart disease: a review of recent developments. Curr Opin Cardiol. 2010; 25, 192–197.Google Scholar
57. Ransom, J, Srivastava, D. The genetics of cardiac birth defects. Semin Cell Dev Biol. 2007; 18, 132–139.Google Scholar
58. Liu, A, et al. Biomechanics of the chick embryonic heart outflow tract at HH18 using 4D optical coherence tomography imaging and computational modeling. PLoS One. 2012; 7, e40869.Google Scholar
59. Midgett, M, Rugonyi, S. Congenital heart malformations induced by hemodynamic altering surgical interventions. Front Physiol. 2014; 5, 287.Google Scholar
60. Hogers, B, et al. Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. Circ Res. 1997; 80, 473–481.Google Scholar
61. Shaut, CA, et al. HOXA13 Is essential for placental vascular patterning and labyrinth endothelial specification. PLoS Genet. 2008; 4, e1000073.Google Scholar
62. Maylie, JG. Excitation-contraction coupling in neonatal and adult myocardium of cat. Am J Physiol. 1982; 242, H834–H843.Google Scholar
63. Woods, LL, Weeks, DA, Rasch, R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004; 65, 1339–1348.Google Scholar
64. Luyckx, VA, Brenner, BM. Birth weight, malnutrition and kidney-associated outcomes-a global concern. Nat Rev Nephrol. 2015; 11, 135–149.CrossRefGoogle ScholarPubMed
65. Jiang, B, et al. Birth weight and cardiac structure in children. Pediatrics. 2006; 117, e257–e261.Google Scholar
66. Sominsky, L, et al. Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety. PLoS One. 2013; 8, e57700.Google Scholar
67. Ward, AM, Phillips, DI. Fetal programming of stress responses. Stress. 2001; 4, 263–271.Google Scholar
68. Leeson, CP, et al. Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation. 2001; 103, 1264–1268.Google Scholar
69. Barker, DJ, et al. Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life. BMJ. 1992; 304, 148–152.Google Scholar
70. Stacy, V, et al. The influence of naturally occurring differences in birthweight on ventricular cardiomyocyte number in sheep. Anat Rec (Hoboken). 2009; 292, 29–37.Google Scholar
71. Barbera, A, et al. Right ventricular systolic pressure load alters myocyte maturation in fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2000; 279, R1157–R1164.Google Scholar
72. Crispi, F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010; 121, 2427–2436.Google Scholar
73. Dodson, RB, et al. Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth-restricted fetal sheep. Pediatr Res. 2013; 73, 147–154.Google Scholar
74. Martyn, CN, Greenwald, SE. A hypothesis about a mechanism for the programming of blood pressure and vascular disease in early life. Clin Exp Pharmacol Physiol. 2001; 28, 948–951.Google Scholar
75. Barker, DJ, et al. Growth in utero and serum cholesterol concentrations in adult life. BMJ. 1993; 307, 1524–1527.Google Scholar
76. Napoli, C, et al. Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation. 2002; 105, 1360–1367.Google Scholar
77. Moisiadis, VG, Matthews, SG. Glucocorticoids and fetal programming part 2: mechanisms. Nat Rev Endocrinol. 2014; 10, 403–411.Google Scholar
78. Giussani, DA, et al. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS One. 2012; 7, e31017.CrossRefGoogle ScholarPubMed
79. Giussani, DA, et al. Heart disease link to fetal hypoxia and oxidative stress. Adv Exp Med Biol. 2014; 814, 77–87.Google Scholar
80. Morrison, JL, et al. Restriction of placental function alters heart development in the sheep fetus. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R306–R313.Google Scholar
81. Bubb, KJ, et al. Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep. J Physiol. 2007; 578, 871–881.Google Scholar
82. Louey, S, et al. Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes. J Physiol. 2007; 580, 639–648.Google Scholar
83. Jonker, SS, et al. Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart. J Appl Physiol (1985). 2007; 102, 1130–1142.Google Scholar
84. Pinson, CW, Morton, MJ, Thornburg, KL. Mild pressure loading alters right ventricular function in fetal sheep. Circ Res. 1991; 68, 947–957.Google Scholar
85. Jonker, SS, et al. Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R913–R919.Google Scholar
86. O’Tierney, PF, et al. Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R573–R578.Google Scholar
87. Fisher, DJ, Heymann, MA, Rudolph, AM. Myocardial oxygen and carbohydrate consumption in fetal lambs in utero and in adult sheep. Am J Physiol. 1980; 238, H399–H405.Google Scholar
88. Davis, L, et al. Augmentation of coronary conductance in adult sheep made anaemic during fetal life. J Physiol. 2003; 547, 53–59.CrossRefGoogle ScholarPubMed
89. Davis, L, Thornburg, KL, Giraud, GD. The effects of anaemia as a programming agent in the fetal heart. J Physiol. 2005; 565, 35–41.Google Scholar
90. Yang, Q, et al. Effect of fetal anaemia on myocardial ischaemia-reperfusion injury and coronary vasoreactivity in adult sheep. Acta Physiol (Oxf). 2008; 194, 325–334.Google Scholar
91. Li, G, et al. Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult rat. J Soc Gynecol Investig. 2003; 10, 265–274.Google Scholar
92. Chattergoon, NN, et al. Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine cardiomyocytes. Am J Physiol Heart Circ Physiol. 2014; 307, H1216–H1225.Google Scholar
93. Giraud, GD, et al. Cortisol stimulates cell cycle activity in the cardiomyocyte of the sheep fetus. Endocrinology. 2006; 147, 3643–3649.Google Scholar
94. Sundgren, NC, et al. Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes. Am J Physiol Regul Integr Comp Physiol. 2003; 285, R1481–R1489.Google Scholar
95. Sundgren, NC, et al. Angiotensin II stimulates hyperplasia but not hypertrophy in immature ovine cardiomyocytes. J Physiol. 2003; 548, 881–891.Google Scholar
96. Chattergoon, NN, et al. Thyroid hormone drives fetal cardiomyocyte maturation. FASEB J. 2012; 26, 397–408.Google Scholar
97. Chattergoon, NN, Giraud, GD, Thornburg, KL. Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro. J Endocrinol. 2007; 192, R1–R8.Google Scholar
98. O’Tierney, PF, et al. Atrial natriuretic peptide inhibits angiotensin II-stimulated proliferation in fetal cardiomyocytes. J Physiol. 2010; 588, 2879–2889.Google Scholar
99. Baschat, AA. Fetal responses to placental insufficiency: an update. BJOG. 2004; 111, 1031–1041.Google Scholar
100. Forhead, AJ, et al. Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term. Endocrinology. 2006; 147, 5988–5994.Google Scholar
101. Patterson, AJ, et al. Chronic prenatal hypoxia induces epigenetic programming of PKC{epsilon} gene repression in rat hearts. Circ Res. 2010; 107, 365–373.Google Scholar
102. Chen, M, Xiong, F, Zhang, L. Promoter methylation of Egr-1 site contributes to fetal hypoxia-mediated PKCepsilon gene repression in the developing heart. Am J Physiol Regul Integr Comp Physiol. 2013; 304, R683–R689.Google Scholar
103. Hata, A. Functions of microRNAs in cardiovascular biology and disease. Annu Rev Physiol. 2013; 75, 69–93.Google Scholar
104. Eulalio, A, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012; 492, 376–381.Google Scholar
105. Tingare, A, Thienpont, B, Roderick, HL. Epigenetics in the heart: the role of histone modifications in cardiac remodelling. Biochem Soc Trans. 2013; 41, 789–796.CrossRefGoogle ScholarPubMed
106. Messer, L. Developmental programming: priming disease susceptibility for subsequent generations. 2015.Google Scholar