Skip to main content

Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches

  • C. Yzydorczyk (a1), J. B. Armengaud (a1), A. C. Peyter (a2), H. Chehade (a1) (a3), F. Cachat (a3), C. Juvet (a1) (a3), B. Siddeek (a1), S. Simoncini (a4), F. Sabatier (a4), F. Dignat-George (a4), D. Mitanchez (a5) (a6) and U. Simeoni (a1)...

Individuals born after intrauterine growth restriction (IUGR) have an increased risk of perinatal morbidity/mortality, and those who survive face long-term consequences such as cardiovascular-related diseases, including systemic hypertension, atherosclerosis, coronary heart disease and chronic kidney disease. In addition to the demonstrated long-term effects of decreased nephron endowment and hyperactivity of the hypothalamic–pituitary–adrenal axis, individuals born after IUGR also exhibit early alterations in vascular structure and function, which have been identified as key factors of the development of cardiovascular-related diseases. The endothelium plays a major role in maintaining vascular function and homeostasis. Therefore, it is not surprising that impaired endothelial function can lead to the long-term development of vascular-related diseases. Endothelial dysfunction, particularly impaired endothelium-dependent vasodilation and vascular remodeling, involves decreased nitric oxide (NO) bioavailability, impaired endothelial NO synthase functionality, increased oxidative stress, endothelial progenitor cells dysfunction and accelerated vascular senescence. Preventive approaches such as breastfeeding, supplementation with folate, vitamins, antioxidants, L-citrulline, L-arginine and treatment with NO modulators represent promising strategies for improving endothelial function, mitigating long-term outcomes and possibly preventing IUGR of vascular origin. Moreover, the identification of early biomarkers of endothelial dysfunction, especially epigenetic biomarkers, could allow early screening and follow-up of individuals at risk of developing cardiovascular and renal diseases, thus contributing to the development of preventive and therapeutic strategies to avert the long-term effects of endothelial dysfunction in infants born after IUGR.

Corresponding author
*Address for correspondence: C. Yzydorczyk, Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 27, 1011 Lausanne, Switzerland.(Email
Hide All

These authors contributed equally to this work.

Hide All
1. Brodsky, D, Christou, H. Current concepts in intrauterine growth restriction. J Intensive Care Med. 2004; 19, 307319.
2. Jang, DG, Jo, YS, Lee, SJ, Kim, N, Lee, GS. Perinatal outcomes and maternal clinical characteristics in IUGR with absent or reversed end-diastolic flow velocity in the umbilical artery. Arch Gynecol Obstet. 2011; 284, 7378.
3. Saleem, T, Sajjad, N, Fatima, S, et al. Intrauterine growth retardation – small events, big consequences. Ital J Pediatr. 2011; 37, 41.
4. Mongelli, M, Gardosi, J. Symphysis-fundus height and pregnancy characteristics in ultrasound-dated pregnancies. Obstet Gynecol. 1999; 94, 591594.
5. Committee on Practice Bulletins--Gynecology ACoO, Gynecologists WDCUSA. Intrauterine growth restriction. Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2001; 72, 8596.
6. Alberry, M, Soothill, P. Management of fetal growth restriction. Arch Dis Child Fetal Neonatal Ed. 2007; 92, F62F67.
7. Figueras, F, Gardosi, J. Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol. 2011; 204, 288300.
8. Barker, ED, McAuliffe, FM, Alderdice, F, et al. The role of growth trajectories in classifying fetal growth restriction. Obstet Gynecol. 2013; 122, 248254.
9. Villar, J, Cheikh Ismail, L, Victora, CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014; 384, 857868.
10. Villar, J, Giuliani, F, Fenton, TR, et al. INTERGROWTH-21st very preterm size at birth reference charts. Lancet. 2016; 387, 844845.
11. Rosario, FJ, Jansson, N, Kanai, Y, et al. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology. 2011; 152, 11191129.
12. Johansson, M, Karlsson, L, Wennergren, M, Jansson, T, Powell, TL. Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction. J Clin Endocrinol Metab. 2003; 88, 28312837.
13. Settle, P, Sibley, CP, Doughty, IM, et al. Placental lactate transporter activity and expression in intrauterine growth restriction. J Soc Gynecol Investig. 2006; 13, 357363.
14. Chaiworapongsa, T, Chaemsaithong, P, Yeo, L, Romero, R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014; 10, 466480.
15. Adams Waldorf, KM, McAdams, RM. Influence of infection during pregnancy on fetal development. Reproduction. 2013; 146, R151R162.
16. Derricott, H, Jones, RL, Heazell, AE. Investigating the association of villitis of unknown etiology with stillbirth and fetal growth restriction – a systematic review. Placenta. 2013; 34, 856862.
17. Baba, S, Wikstrom, AK, Stephansson, O, Cnattingius, S. Changes in snuff and smoking habits in Swedish pregnant women and risk for small for gestational age births. BJOG. 2013; 120, 456462.
18. Maruyama, H, Shinozuka, M, Kondoh, Y, et al. Thrombocytopenia in preterm infants with intrauterine growth restriction. Acta Med Okayama. 2008; 62, 313317.
19. Hall, JG. Review and hypothesis: syndromes with severe intrauterine growth restriction and very short stature – are they related to the epigenetic mechanism(s) of fetal survival involved in the developmental origins of adult health and disease? Am J Med Genet A. 2010; 152A, 512527.
20. Malik, S, Cleves, MA, Zhao, W, et al. Association between congenital heart defects and small for gestational age. Pediatrics. 2007; 119, e976e982.
21. Hillman, S, Peebles, DM, Williams, DJ. Paternal metabolic and cardiovascular risk factors for fetal growth restriction: a case-control study. Diabetes Care. 2013; 36, 16751680.
22. Li, J, Tsuprykov, O, Yang, X, Hocher, B. Paternal programming of offspring cardiometabolic diseases in later life. J Hypertens. 2016; 34, 21112126.
23. Minshall, RD, Tiruppathi, C, Vogel, SM, Malik, AB. Vesicle formation and trafficking in endothelial cells and regulation of endothelial barrier function. Histochem Cell Biol. 2002; 117, 105112.
24. Purnomowati, A, Kariadi, SH, Achmad, TH, Mose, JC, Setianto, B. Endothelial dysfunction in the young adult: a retrospective cohort study on the effect of low birth weight. Acta Med Indones. 2014; 46, 111116.
25. Bassareo, PP, Fanos, V, Puddu, M, et al. Reduced brachial flow-mediated vasodilation in young adult ex extremely low birth weight preterm: a condition predictive of increased cardiovascular risk? J Matern Fetal Neonatal Med. 2010; 23(Suppl. 3), 121124.
26. Martin, H, Lindblad, B, Norman, M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007; 119, 11521158.
27. Leeson, P, Thorne, S, Donald, A, et al. Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart. 1997; 78, 2227.
28. Leeson, C, Whincup, P, Cook, D, et al. Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors. Circulation. 1997; 96, 22332238.
29. Goodfellow, J, Bellamy, MF, Gorman, ST, et al. Endothelial function is impaired in fit young adults of low birth weight. Cardiovasc Res. 1998; 40, 600606.
30. Leeson, C, Kattenhorn, M, Morley, R, Lucas, A, Deanfield, J. Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation. 2001; 103, 12641268.
31. Krause, BJ, Carrasco-Wong, I, Caniuguir, A, et al. Endothelial eNOS/arginase imbalance contributes to vascular dysfunction in IUGR umbilical and placental vessels. Placenta. 2013; 34, 2028.
32. Yzydorczyk, C, Gobeil, F Jr, Cambonie, G, et al. Exaggerated vasomotor response to ANG II in rats with fetal programming of hypertension associated with exposure to a low-protein diet during gestation. Am J Physiol Regul Integr Comp Physiol. 2006; 291, R1060R1068.
33. Pladys, P, Sennlaub, F, Brault, S, et al. Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R1580R1588.
34. Brawley, L, Itoh, S, Torrens, C, et al. Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring. Pediatr Res. 2003; 54, 8390.
35. Franco, MC, Arruda, R, Dantas, A, et al. Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring. Cardiovasc Res. 2002; 56, 145153.
36. Tare, M, Parkington, HC, Wallace, EM, et al. Maternal melatonin administration mitigates coronary stiffness and endothelial dysfunction, and improves heart resilience to insult in growth restricted lambs. J Physiol. 2014; 592, 26952709.
37. Borwick, SC, Rhind, SM, McMillen, SR, Racey, PA. Effect of undernutrition of ewes from the time of mating on fetal ovarian development in mid gestation. Reprod Fertil Dev. 1997; 9, 711715.
38. Hurtado, R, Celani, M, Geber, S. Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial. Climacteric. 2016; 19, 448451.
39. Gleeson, M, Bishop, NC, Stensel, DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011; 11, 607615.
40. Leinonen, E, Hurt-Camejo, E, Wiklund, O, et al. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis. 2003; 166, 387394.
41. Pellanda, LC, Duncan, BB, Vigo, A, et al. Low birth weight and markers of inflammation and endothelial activation in adulthood: the ARIC study. Int J Cardiol. 2009; 134, 371377.
42. Teeninga, N, Schreuder, MF, Bokenkamp, A, Delemarre-van de Waal, HA, van Wijk, JA. Influence of low birth weight on minimal change nephrotic syndrome in children, including a meta-analysis. Nephrol Dial Transplant. 2008; 23, 16151620.
43. Skilton, MR, Evans, N, Griffiths, KA, Harmer, JA, Celermajer, DS. Aortic wall thickness in newborns with intrauterine growth restriction. Lancet. 2005; 365, 14841486.
44. Koklu, E, Ozturk, MA, Gunes, T, Akcakus, M, Kurtoglu, S. Is increased intima-media thickness associated with preatherosclerotic changes in intrauterine growth restricted newborns? Acta Paediatr. 2007; 96, 1858; author reply 1859.
45. Litwin, M, Niemirska, A. Intima-media thickness measurements in children with cardiovascular risk factors. Pediatr Nephrol. 2009; 24, 707719.
46. Cosmi, E, Visentin, S, Fanelli, T, Mautone, AJ, Zanardo, V. Aortic intima media thickness in fetuses and children with intrauterine growth restriction. Obstet Gynecol. 2009; 114, 11091114.
47. Crispi, F, Figueras, F, Cruz-Lemini, M, et al. Cardiovascular programming in children born small for gestational age and relationship with prenatal signs of severity. Am J Obstet Gynecol. 2012; 207, 121 e121121 e129.
48. Crispi, F, Bijnens, B, Figueras, F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010; 121, 24272436.
49. Oren, A, Vos, LE, Uiterwaal, CS, et al. Birth weight and carotid intima-media thickness: new perspectives from the atherosclerosis risk in young adults (ARYA) study. Ann Epidemiol. 2004; 14, 816.
50. Jensen, GM, Moore, LG. The effect of high altitude and other risk factors on birthweight: independent or interactive effects? Am J Public Health. 1997; 87, 10031007.
51. Lueder, FL, Kim, SB, Buroker, CA, Bangalore, SA, Ogata, ES. Chronic maternal hypoxia retards fetal growth and increases glucose utilization of select fetal tissues in the rat. Metabolism. 1995; 44, 532537.
52. Barker, DJ. The fetal origins of coronary heart disease. Acta Paediatr Suppl. 1997; 422, 7882.
53. Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564567.
54. Giaccia, AJ, Simon, MC, Johnson, R. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev. 2004; 18, 21832194.
55. Malamitsi-Puchner, A, Boutsikou, T, Economou, E, et al. Angiopoietin-2 in the perinatal period and the role of intrauterine growth restriction. Acta Obstet Gynecol Scand. 2006; 85, 4548.
56. Griendling, KK, Harrison, DG. Dual role of reactive oxygen species in vascular growth. Circ Res. 1999; 85, 562563.
57. Irani, K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res. 2000; 87, 179183.
58. Touyz, RM, Schiffrin, EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol. 2004; 122, 339352.
59. Ushio-Fukai, M, Zafari, AM, Fukui, T, Ishizaka, N, Griendling, KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem. 1996; 271, 2331723321.
60. Griendling, KK, Minieri, CA, Ollerenshaw, JD, Alexander, RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res. 1994; 74, 11411148.
61. Zafari, AM, Ushio-Fukai, M, Akers, M, et al. Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension. 1998; 32, 488495.
62. Tyagi, SC, Simon, SR. Regulation of neutrophil elastase activity by elastin-derived peptide. J Biol Chem. 1993; 268, 1651316518.
63. Chow, AK, Cena, J, Schulz, R. Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature. Br J Pharmacol. 2007; 152, 189205.
64. Rajagopalan, S, Meng, XP, Ramasamy, S, Harrison, DG, Galis, ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996; 98, 25722579.
65. Sesso, R, Franco, MC. Abnormalities in metalloproteinase pathways and IGF-I axis: a link between birth weight, hypertension, and vascular damage in childhood. Am J Hypertens. 2010; 23, 611.
66. Huyard, F, Yzydorczyk, C, Castro, MM, et al. Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk. PLoS One. 2014; 9, e92287.
67. Yzydorczyk, C, Comte, B, Cambonie, G, et al. Neonatal oxygen exposure in rats leads to cardiovascular and renal alterations in adulthood. Hypertension. 2008; 52, 889895.
68. Mivelaz, Y YC, Barbier, A, Cloutier, A, Fouron, JC, Nuyt, AM. Neonatal oxygen exposure leads to increased aortic wall stiffness in adult rats: a Doppler ultrasound study. J Dev Orig Health Dis. 2011; 2, 184189.
69. Chatterjee, A, Black, SM, Catravas, JD. Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascul Pharmacol. 2008; 49, 134140.
70. Förstermann, U, Münzel, T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006; 113, 17081714.
71. Searles, CD. Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression. Am J Physiol Cell Physiol. 2006; 291, C803C816.
72. De Caterina, R, Libby, P, Peng, HB, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995; 96, 6068.
73. Hata, T, Hashimoto, M, Manabe, A, et al. Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants. Hum Reprod. 1998; 13, 10701073.
74. Singh, S, Singh, A, Sharma, D, et al. Effect of L-arginine on nitric oxide levels in intrauterine growth restriction and its correlation with fetal outcome. Indian J Clin Biochem. 2015; 30, 298304.
75. Lyall, F, Greer, IA, Young, A, Myatt, L. Nitric oxide concentrations are increased in the feto-placental circulation in intrauterine growth restriction. Placenta. 1996; 17, 165168.
76. Myatt, L, Eis, AL, Brockman, DE, Greer, IA, Lyall, F. Endothelial nitric oxide synthase in placental villous tissue from normal, pre-eclamptic and intrauterine growth restricted pregnancies. Hum Reprod. 1997; 12, 167172.
77. Payne, JA, Alexander, BT, Khalil, RA. Reduced endothelial vascular relaxation in growth-restricted offspring of pregnant rats with reduced uterine perfusion. Hypertension. 2003; 42, 768774.
78. Sathishkumar, K, Elkins, R, Yallampalli, U, Yallampalli, C. Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring. J Vasc Res. 2009; 46, 229239.
79. Bourdon, A, Parnet, P, Nowak, C, et al. l-Citrulline supplementation enhances fetal growth and protein synthesis in rats with intrauterine growth restriction. J Nutr. 2016; 146, 532541.
80. Sathishkumar, K, Elkins, R, Yallampalli, U, Balakrishnan, M, Yallampalli, C. Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero. Early Hum Dev. 2011; 87, 407414.
81. Hracsko, Z, Hermesz, E, Ferencz, A, et al. Endothelial nitric oxide synthase is up-regulated in the umbilical cord in pregnancies complicated with intrauterine growth retardation. In Vivo. 2009; 23, 727732.
82. Dellee, U, Tobias, S, Li, H, Mildenberger, E. Expression of NO synthases and redox enzymes in umbilical arteries from newborns born small, appropriate, and large for gestational age. Pediatr Res. 2013; 73, 142146.
83. Takushima, S, Nishi, Y, Nonoshita, A, et al. Changes in the nitric oxide-soluble guanylate cyclase system and natriuretic peptide receptor system in placentas of pregnant Dahl salt-sensitive rats. J Obstet Gynaecol Res. 2015; 41, 540550.
84. Arroyo, JA, Anthony, RV, Parker, TA, Galan, HL. eNOS, NO, and the activation of ERK and AKT signaling at mid-gestation and near-term in an ovine model of intrauterine growth restriction. Syst Biol Reprod Med. 2010; 56, 6273.
85. Tolbert, T, Thompson, JA, Bouchard, P, Oparil, S. Estrogen-induced vasoprotection is independent of inducible nitric oxide synthase expression: evidence from the mouse carotid artery ligation model. Circulation. 2001; 104, 27402745.
86. Krause, BJ, Costello, PM, Munoz-Urrutia, E, et al. Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses. Epigenetics. 2013; 8, 944952.
87. Laskowska, M, Laskowska, K, Oleszczuk, J. Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction. Hypertens Pregnancy. 2013; 32, 8393.
88. Gumus, E, Atalay, MA, Cetinkaya Demir, B, Sahin Gunes, E. Possible role of asymmetric dimethylarginine (ADMA) in prediction of perinatal outcome in preeclampsia and fetal growth retardation related to preeclampsia. J Matern Fetal Neonatal Med. 2016; 29, 38063811.
89. Rizos, D, Eleftheriades, M, Batakis, E, et al. Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby. J Matern Fetal Neonatal Med. 2012; 25, 13111315.
90. Post, MS, Verhoeven, MO, van der Mooren, MJ, et al. Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women. J Clin Endocrinol Metab. 2003; 88, 42214226.
91. Karkanaki, A, Vavilis, D, Traianos, A, Kalogiannidis, I, Panidis, D. Hormone therapy and asymmetrical dimethylarginine in postmenopausal women. Hormones (Athens). 2010; 9, 127135.
92. Yu, XJ, Li, YJ, Xiong, Y. Increase of an endogenous inhibitor of nitric oxide synthesis in serum of high cholesterol fed rabbits. Life Sci. 1994; 54, 753758.
93. Boger, RH, Bode-Boger, SM, Sydow, K, Heistad, DD, Lentz, SR. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2000; 20, 15571564.
94. Griendling, KK, FitzGerald, GA. Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003; 108, 19121916.
95. Burton, GJ, Jauniaux, E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2011; 25, 287299.
96. Takagi, Y, Nikaido, T, Toki, T, et al. Levels of oxidative stress and redox-related molecules in the placenta in preeclampsia and fetal growth restriction. Virchows Arch. 2004; 444, 4955.
97. Maisonneuve, E, Delvin, E, Edgard, A, et al. Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies. J Matern Fetal Neonatal Med. 2015; 28, 14711475.
98. Webster, RP, Roberts, VH, Myatt, L. Protein nitration in placenta – functional significance. Placenta. 2008; 29, 985994.
99. Kossenjans, W, Eis, A, Sahay, R, Brockman, D, Myatt, L. Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia. Am J Physiol Heart Circ Physiol. 2000; 278, H1311H1319.
100. Santilli, F, D’Ardes, D, Davi, G. Oxidative stress in chronic vascular disease: from prediction to prevention. Vascul Pharmacol. 2015; 74, 2337.
101. Yzydorczyk, C, Comte, B, Huyard, F, et al. Developmental programming of eNOS uncoupling and enhanced vascular oxidative stress in adult rats after transient neonatal oxygen exposure. J Cardiovasc Pharmacol. 2013; 61, 816.
102. Vasquez-Vivar, J, Kalyanaraman, B, Martasek, P, et al. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A. 1998; 95, 92209225.
103. d’Uscio, LV, Santhanam, AV, Katusic, ZS. Erythropoietin prevents endothelial dysfunction in GTP-cyclohydrolase I-deficient hph1 mice. J Cardiovasc Pharmacol. 2014; 64, 514521.
104. Yang, YM, Huang, A, Kaley, G, Sun, D. eNOS uncoupling and endothelial dysfunction in aged vessels. Am J Physiol Heart Circ Physiol. 2009; 297, H1829H1836.
105. Landmesser, U, Dikalov, S, Price, SR, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003; 111, 12011209.
106. Chalupsky, K, Cai, H. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2005; 102, 90569061.
107. Sydow, K, Munzel, T. ADMA and oxidative stress. Atheroscler Suppl. 2003; 4, 4151.
108. Schneider, D, Hernandez, C, Farias, M, et al. Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA. Placenta. 2015; 36, 552558.
109. Mitchell, BM, Cook, LG, Danchuk, S, Puschett, JB. Uncoupled endothelial nitric oxide synthase and oxidative stress in a rat model of pregnancy-induced hypertension. Am J Hypertens. 2007; 20, 12971304.
110. Oliveira, V, Akamine, EH, Carvalho, MH, et al. Influence of aerobic training on the reduced vasoconstriction to angiotensin II in rats exposed to intrauterine growth restriction: possible role of oxidative stress and AT2 receptor of angiotensin II. PLoS One. 2014; 9, e113035.
111. Asahara, T, Murohara, T, Sullivan, A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275, 964967.
112. Yoder, MC, Mead, LE, Prater, D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007; 109, 18011809.
113. Purhonen, S, Palm, J, Rossi, D, et al. Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth. Proc Natl Acad Sci U S A. 2008; 105, 66206625.
114. Hill, JM, Zalos, G, Halcox, JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348, 593600.
115. Sipos, PI, Crocker, IP, Hubel, CA, Baker, PN. Endothelial progenitor cells: their potential in the placental vasculature and related complications. Placenta. 2010; 31, 110.
116. Hwang, HS, Kwon, YG, Kwon, JY, et al. Senescence of fetal endothelial progenitor cell in pregnancy with idiopathic fetal growth restriction. J Matern Fetal Neonatal Med. 2012; 25, 17691773.
117. Ligi, I, Simoncini, S, Tellier, E, et al. A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants. Blood. 2011; 118, 16991709.
118. Ligi, I, Simoncini, S, Tellier, E, et al. Altered angiogenesis in low birth weight individuals: a role for anti-angiogenic circulating factors. J Matern Fetal Neonatal Med. 2014; 27, 233238.
119. Minamino, T, Komuro, I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007; 100, 1526.
120. Erusalimsky, JD, Fenton, M. Further in vivo evidence that cellular senescence is implicated in vascular pathophysiology. Circulation. 2002; 106, e144; author reply e144.
121. Borradaile, NM, Pickering, JG. NAD(+), sirtuins, and cardiovascular disease. Curr Pharm Des. 2009; 15, 110117.
122. Ota, H, Akishita, M, Eto, M, et al. Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol. 2007; 43, 571579.
123. Vassallo, PF, Simoncini, S, Ligi, I, et al. Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression. Blood. 2014; 123, 21162126.
124. Fattal-Valevski, A, Bernheim, J, Leitner, Y, et al. Blood pressure values in children with intrauterine growth retardation. Isr Med Assoc J. 2001; 3, 805808.
125. Rossi, P, Tauzin, L, Marchand, E, et al. Respective roles of preterm birth and fetal growth restriction in blood pressure and arterial stiffness in adolescence. J Adolesc Health. 2011; 48, 520522.
126. Chiolero, A, Cachat, F, Burnier, M, Paccaud, F, Bovet, P. Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight. J Hypertens. 2007; 25, 22092217.
127. Leon, DA, Johansson, M, Rasmussen, F. Gestational age and growth rate of fetal mass are inversely associated with systolic blood pressure in young adults: an epidemiologic study of 165,136 Swedish men aged 18 years. Am J Epidemiol. 2000; 152, 597604.
128. Nilsson, PM, Ostergren, PO, Nyberg, P, Soderstrom, M, Allebeck, P. Low birth weight is associated with elevated systolic blood pressure in adolescence: a prospective study of a birth cohort of 149378 Swedish boys. J Hypertens. 1997; 15, 16271631.
129. Gennser, G, Rymark, P, Isberg, PE. Low birth weight and risk of high blood pressure in adulthood. Br Med J (Clin Res Ed). 1988; 296, 14981500.
130. Martyn, CN, Barker, DJ, Jespersen, S, et al. Growth in utero, adult blood pressure, and arterial compliance. Br Heart J. 1995; 73, 116121.
131. Curhan, GC, Willett, WC, Rimm, EB, et al. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation. 1996; 94, 32463250.
132. Law, CM, Shiell, AW. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens. 1996; 14, 935941.
133. Huxley, R, Neil, A, Collins, R. Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Lancet. 2002; 360, 659665.
134. Tauzin, L, Rossi, P, Grosse, C, et al. Increased systemic blood pressure and arterial stiffness in young adults born prematurely. J Dev Orig Health Dis. 2014; 5, 448452.
135. Wlodek, ME, Westcott, K, Siebel, AL, Owens, JA, Moritz, KM. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008; 74, 187195.
136. Alexander, BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension. 2003; 41, 457462.
137. Bourque, SL, Gragasin, FS, Quon, AL, et al. Prenatal hypoxia causes long-term alterations in vascular endothelin-1 function in aged male, but not female, offspring. Hypertension. 2013; 62, 753758.
138. Ortiz, LA, Quan, A, Zarzar, F, Weinberg, A, Baum, M. Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension. 2003; 41, 328334.
139. Mossa, F, Carter, F, Walsh, SW, et al. Maternal undernutrition in cows impairs ovarian and cardiovascular systems in their offspring. Biol Reprod. 2013; 88, 92.
140. Goyal, R, Van-Wickle, J, Goyal, D, Longo, LD. Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually dimorphic programming of hypertension. BMC Physiol. 2015; 15, 2.
141. Gilbert, JS, Lang, AL, Grant, AR, Nijland, MJ. Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol. 2005; 565, 137147.
142. Ozaki, T, Nishina, H, Hanson, M, Poston, L. Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol. 2001; 530, 141152.
143. Cambonie, G, Comte, B, Yzydorczyk, C, et al. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1236R1245.
144. Taddei, S, Virdis, A, Mattei, P, Arzilli, F, Salvetti, A. Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension. J Cardiovasc Pharmacol. 1992; 20(Suppl. 12), S193S195.
145. Miller, MJ, Pinto, A, Mullane, KM. Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension. Hypertension. 1987; 10, 164170.
146. d’Uscio, LV, Barton, M, Shaw, S, Moreau, P, Luscher, TF. Structure and function of small arteries in salt-induced hypertension: effects of chronic endothelin-subtype-A-receptor blockade. Hypertension. 1997; 30, 905911.
147. Verma, S, Anderson, TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002; 105, 546549.
148. Ludmer, PL, Selwyn, AP, Shook, TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986; 315, 10461051.
149. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341, 938941.
150. Leon, DA, Lithell, HO, Vagero, D, 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, 241245.
151. Wang, SF, Shu, L, Sheng, J, et al. Birth weight and risk of coronary heart disease in adults: a meta-analysis of prospective cohort studies. J Dev Orig Health Dis. 2014; 5, 408419.
152. Eriksson, M, Tibblin, G, Cnattingius, S. Low birthweight and ischaemic heart disease. Lancet. 1994; 343, 731.
153. Banci, M, Saccucci, P, Dofcaci, A, et al. Birth weight and coronary artery disease. The effect of gender and diabetes. Int J Biol Sci. 2009; 5, 244248.
154. Abrahamson, DR, Robert, B, Hyink, DP, St John, PL, Daniel, TO. Origins and formation of microvasculature in the developing kidney. Kidney Int Suppl. 1998; 67, S7S11.
155. Hyink, DP, Tucker, DC, St John, PL, et al. Endogenous origin of glomerular endothelial and mesangial cells in grafts of embryonic kidneys. Am J Physiol. 1996; 270, F886F899.
156. Stehouwer, CD, Henry, RM, Dekker, JM, et al. Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction – the Hoorn Study. Kidney Int Suppl. 2004; 66, S42S44.
157. Pedrinelli, R, Giampietro, O, Carmassi, F, et al. Microalbuminuria and endothelial dysfunction in essential hypertension. Lancet. 1994; 344, 1418.
158. Mancuso, P, Antoniotti, P, Quarna, J, et al. Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses. Clin Cancer Res. 2009; 15, 267273.
159. Perticone, F, Maio, R, Perticone, M, et al. Endothelial dysfunction and subsequent decline in glomerular filtration rate in hypertensive patients. Circulation. 2010; 122, 379384.
160. Gris, JC, Branger, B, Vecina, F, et al. Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. Kidney Int. 1994; 46, 807813.
161. Manalich, R, Reyes, L, Herrera, M, Melendi, C, Fundora, I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000; 58, 770773.
162. White, SL, Perkovic, V, Cass, A, et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis. 2009; 54, 248261.
163. Giapros, V, Papadimitriou, P, Challa, A, Andronikou, S. The effect of intrauterine growth retardation on renal function in the first two months of life. Nephrol Dial Transplant. 2007; 22, 96103.
164. Silverwood, RJ, Pierce, M, Hardy, R, et al. Low birth weight, later renal function, and the roles of adulthood blood pressure, diabetes, and obesity in a British birth cohort. Kidney Int. 2013; 84, 12621270.
165. Vehaskari, VM, Aviles, DH, Manning, J. Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59, 238245.
166. Woods, LL, Ingelfinger, JR, Nyengaard, JR, Rasch, R. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49, 460467.
167. Boubred, F, Delamaire, E, Buffat, C, et al. High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR. Pediatr Res. 2016; 79, 2226.
168. Boubred, F, Buffat, C, Feuerstein, JM, et al. Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats. Am J Physiol Renal Physiol. 2007; 293, F1944F1949.
169. Boubred, F, Daniel, L, Buffat, C, et al. Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats. Am J Physiol Renal Physiol. 2009; 297, F943F951.
170. Anderson, S, King, AJ, Brenner, BM. Hyperlipidemia and glomerular sclerosis: an alternative viewpoint. Am J Med. 1989; 87, 34N38N.
171. Ikeda, Y, Tajima, S, Izawa-Ishizawa, Y, et al. Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia. J Cardiovasc Pharmacol. 2013; 61, 423429.
172. Safaeian, L, Javanmard, SH, Mollanoori, Y, Dana, N. Cytoprotective and antioxidant effects of human lactoferrin against H2O2-induced oxidative stress in human umbilical vein endothelial cells. Adv Biomed Res. 2015; 4, 188.
173. Verhaar, MC, Stroes, E, Rabelink, TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002; 22, 613.
174. Robinson, K, Arheart, K, Refsum, H, et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation. 1998; 97, 437443.
175. Antoniades, C, Shirodaria, C, Warrick, N, et al. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006; 114, 11931201.
176. Xia, XS, Li, X, Wang, L, et al. Supplementation of folic acid and vitamin B(1)(2) reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke. J Clin Neurosci. 2014; 21, 15861590.
177. Wu, CJ, Wang, L, Li, X, et al. Impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine and asymmetric dimethylarginine levels of essential hypertension patients. Zhonghua Xin Xue Guan Bing Za Zhi. 2012; 40, 10031008.
178. Li, JM, Qu, PF, Dang, SN, et al. Effect of folic acid supplementation in childbearing aged women during pregnancy on neonate birth weight in Shaanxi province. Zhonghua Liu Xing Bing Xue Za Zhi. 2016; 37, 10171020.
179. Alessio, AC, Santos, CX, Debbas, V, et al. Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice. Exp Mol Pathol. 2011; 90, 4550.
180. Torrens, C, Brawley, L, Anthony, FW, et al. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006; 47, 982987.
181. Stroes, ES, van Faassen, EE, Yo, M, et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res. 2000; 86, 11291134.
182. Zingg, JM, Azzi, A. Non-antioxidant activities of vitamin E. Curr Med Chem. 2004; 11, 11131133.
183. Wu, D, Liu, L, Meydani, M, Meydani, SN. Vitamin E increases production of vasodilator prostanoids in human aortic endothelial cells through opposing effects on cyclooxygenase-2 and phospholipase A2. J Nutr. 2005; 135, 18471853.
184. Tran, K, Chan, AC. R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule. Biochim Biophys Acta. 1990; 1043, 189197.
185. Memon, S, Pratten, MK. Developmental toxicity of ethanol in chick heart in ovo and in micromass culture can be prevented by addition of vitamin C and folic acid. Reprod Toxicol. 2009; 28, 262269.
186. Hovdenak, N, Haram, K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012; 164, 127132.
187. Sesso, HD, Buring, JE, Christen, WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2008; 300, 21232133.
188. Rumbold, A, Ota, E, Nagata, C, Shahrook, S, Crowther, CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015; 29, CD004072.
189. Rumbold, AR, Crowther, CA, Haslam, RR, et al. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006; 354, 17961806.
190. Care, AS, Sung, MM, Panahi, S, et al. Perinatal resveratrol supplementation to spontaneously hypertensive rat dams mitigates the development of hypertension in adult offspring. Hypertension. 2016; 67, 10381044.
191. Vaziri, ND, Ding, Y, Ni, Z, Gonick, HC. Altered nitric oxide metabolism and increased oxygen free radical activity in lead-induced hypertension: effect of lazaroid therapy. Kidney Int. 1997; 52, 10421046.
192. Vaziri, ND, Ni, Z, Oveisi, F, Trnavsky-Hobbs, DL. Effect of antioxidant therapy on blood pressure and NO synthase expression in hypertensive rats. Hypertension. 2000; 36, 957964.
193. Herrera, EA, Cifuentes-Zuniga, F, Figueroa, E, et al. N-acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs. J Physiol. 2017, 595, 10771092.
194. Hardeland, R, Cardinali, DP, Srinivasan, V, et al. Melatonin – a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011; 93, 350384.
195. Reiter, RJ, Tan, DX, Terron, MP, Flores, LJ, Czarnocki, Z. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim Pol. 2007; 54, 19.
196. Franco Mdo, C, Akamine, EH, Aparecida de Oliveira, M, et al. Vitamins C and E improve endothelial dysfunction in intrauterine-undernourished rats by decreasing vascular superoxide anion concentration. J Cardiovasc Pharmacol. 2003; 42, 211217.
197. Galano, A, Tan, DX, Reiter, RJ. On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res. 2013; 54, 245257.
198. Lopez, A, Garcia, JA, Escames, G, et al. Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res. 2009; 46, 188198.
199. Herrera, EA, Macchiavello, R, Montt, C, et al. Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs. J Pineal Res. 2014; 57, 3342.
200. Weekley, LB. Effects of melatonin on isolated pulmonary artery and vein: role of the vascular endothelium. Pulm Pharmacol. 1993; 6, 149154.
201. Girouard, H, Chulak, C, Lejossec, M, Lamontagne, D, de Champlain, J. Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats. J Hypertens. 2001; 19, 13691377.
202. Das, R, Balonan, L, Ballard, HJ, Ho, S. Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery. Int J Cardiol. 2008; 126, 340345.
203. Curis, E, Nicolis, I, Moinard, C, et al. Almost all about citrulline in mammals. Amino Acids. 2005; 29, 177205.
204. Romero, MJ, Platt, DH, Caldwell, RB, Caldwell, RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006; 24, 275290.
205. Chien, SJ, Lin, KM, Kuo, HC, et al. Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate. Transl Res. 2014; 163, 4352.
206. Figueroa, A, Trivino, JA, Sanchez-Gonzalez, MA, Vicil, F. Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens. 2010; 23, 1216.
207. Xuan, C, Lun, LM, Zhao, JX, et al. L-citrulline for protection of endothelial function from ADMA-induced injury in porcine coronary artery. Sci Rep. 2015; 5, 10987.
208. Chen, J, Gong, X, Chen, P, Luo, K, Zhang, X. Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis. BMC Pregnancy Childbirth. 2016; 16, 225.
209. Gui, S, Jia, J, Niu, X, et al. Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review. J Renin Angiotensin Aldosterone Syst. 2014; 15, 8896.
210. Vadillo-Ortega, F, Perichart-Perera, O, Espino, S, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011; 342, d2901.
211. Wu, G, Bazer, FW, Cudd, TA, et al. Pharmacokinetics and safety of arginine supplementation in animals. J Nutr. 2007; 137, 1673S1680S.
212. Dastjerdi, MV, Hosseini, S, Bayani, L. Sildenafil citrate and uteroplacental perfusion in fetal growth restriction. J Res Med Sci. 2012; 17, 632636.
213. Wareing, M, Myers, JE, O’Hara, M, Baker, PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab. 2005; 90, 25502555.
214. Lassala, A, Bazer, FW, Cudd, TA, et al. Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes. J Nutr. 2010; 140, 12421248.
215. Herraiz, S, Pellicer, B, Serra, V, et al. Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats. BJOG. 2012; 119, 13941402.
216. Refuerzo, JS, Sokol, RJ, Aranda, JV, et al. Sildenafil citrate and fetal outcome in pregnant rats. Fetal Diagn Ther. 2006; 21, 259263.
217. Cutfield, WS, Hofman, PL, Mitchell, M, Morison, IM. Could epigenetics play a role in the developmental origins of health and disease? Pediatr Res. 2007; 61, 68R75R.
218. Chen, M, Zhang, L. Epigenetic mechanisms in developmental programming of adult disease. Drug Discov Today. 2011; 16, 10071018.
219. McKay, JA, Mathers, JC. Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf). 2011; 202, 103118.
220. Kangaspeska, S, Stride, B, Metivier, R, et al. Transient cyclical methylation of promoter DNA. Nature. 2008; 452, 112115.
221. Lorenzen, JM, Martino, F, Thum, T. Epigenetic modifications in cardiovascular disease. Basic Res Cardiol. 2012; 107, 245.
222. Ito, S, D’Alessio, AC, Taranova, OV, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010; 466, 11291133.
223. Kriaucionis, S, Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009; 324, 929930.
224. Postberg, J, Kanders, M, Forcob, S, et al. CpG signalling, H2A.Z/H3 acetylation and microRNA-mediated deferred self-attenuation orchestrate foetal NOS3 expression. Clin Epigenetics. 2015; 7, 9.
225. Canani, RB, Costanzo, MD, Leone, L, et al. Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev. 2011; 24, 198205.
226. Xu, XF, Xu, SS, Fu, LC, et al. Epigenetic changes in peripheral leucocytes as biomarkers in intrauterine growth retardation rat. Biomed Rep. 2016; 5, 548552.
227. Shruti, K, Shrey, K, Vibha, R. Micro RNAs: tiny sequences with enormous potential. Biochem Biophys Res Commun. 2011; 407, 445449.
228. Sayed, D, Abdellatif, M. MicroRNAs in development and disease. Physiol Rev. 2011; 91, 827887.
229. Weber, M, Baker, MB, Moore, JP, Searles, CD. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun. 2010; 393, 643648.
230. Fleissner, F, Jazbutyte, V, Fiedler, J, et al. Short communication: asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism. Circ Res. 2010; 107, 138143.
231. Liu, X, Cheng, Y, Yang, J, Xu, L, Zhang, C. Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application. J Mol Cell Cardiol. 2012; 52, 245255.
232. Suarez, Y, Fernandez-Hernando, C, Pober, JS, Sessa, WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007; 100, 11641173.
233. Xu, Q, Seeger, FH, Castillo, J, et al. Micro-RNA-34a contributes to the impaired function of bone marrow-derived mononuclear cells from patients with cardiovascular disease. J Am Coll Cardiol. 2012; 59, 21072117.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed