Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-01-11T12:40:32.787Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  02 May 2017

C. Yzydorczyk ,
J. B. Armengaud ,
A. C. Peyter ,
H. Chehade ,
F. Cachat ,
C. Juvet ,
B. Siddeek ,
S. Simoncini ,
F. Sabatier  and
F. Dignat-George
...Show all authors
C. Yzydorczyk*
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
J. B. Armengaud
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
A. C. Peyter
Affiliation:
Department Woman-Mother-Child, Clinic of Neonatology, Neonatal Research Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
H. Chehade
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Department Woman-Mother-Child, Clinic of Pediatrics, Division of Pediatric Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
F. Cachat
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, Division of Pediatric Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
C. Juvet
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland Department Woman-Mother-Child, Clinic of Pediatrics, Division of Pediatric Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
B. Siddeek
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
S. Simoncini
Affiliation:
VRCM, Aix Marseille University, UMR S INSERM 1076, Faculté de Pharmacie, Marseille, France
F. Sabatier
Affiliation:
VRCM, Aix Marseille University, UMR S INSERM 1076, Faculté de Pharmacie, Marseille, France
F. Dignat-George
Affiliation:
VRCM, Aix Marseille University, UMR S INSERM 1076, Faculté de Pharmacie, Marseille, France
D. Mitanchez
Affiliation:
Division of Neonatology, Department of Perinatology, Armand Trousseau Hospital, APHP, Paris, France Sorbonne University, UPMC University Paris 06, Paris, France
U. Simeoni
Affiliation:
Department Woman-Mother-Child, Clinic of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
*
*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 catherine.yzydorczyk@chuv.ch)
Get access Rights & Permissions [Opens in a new window]

Abstract

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.

Keywords

cardiovascular diseasechronic renal diseasesDOHaDendothelial dysfunctionintrauterine growth restriction
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 4: Themed Issue: Assisted Reproductive Treatments (ART) and DOHAD , August 2017 , pp. 448 - 464
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

These authors contributed equally to this work.

References

1. Brodsky, D, Christou, H. Current concepts in intrauterine growth restriction. J Intensive Care Med. 2004; 19, 307–319.CrossRefGoogle ScholarPubMed
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, 73–78.CrossRefGoogle ScholarPubMed
3. Saleem, T, Sajjad, N, Fatima, S, et al. Intrauterine growth retardation – small events, big consequences. Ital J Pediatr. 2011; 37, 41.CrossRefGoogle ScholarPubMed
4. Mongelli, M, Gardosi, J. Symphysis-fundus height and pregnancy characteristics in ultrasound-dated pregnancies. Obstet Gynecol. 1999; 94, 591–594.Google ScholarPubMed
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, 85–96.Google Scholar
6. Alberry, M, Soothill, P. Management of fetal growth restriction. Arch Dis Child Fetal Neonatal Ed. 2007; 92, F62–F67.CrossRefGoogle ScholarPubMed
7. Figueras, F, Gardosi, J. Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol. 2011; 204, 288–300.CrossRefGoogle ScholarPubMed
8. Barker, ED, McAuliffe, FM, Alderdice, F, et al. The role of growth trajectories in classifying fetal growth restriction. Obstet Gynecol. 2013; 122, 248–254.CrossRefGoogle ScholarPubMed
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, 857–868.CrossRefGoogle ScholarPubMed
10. Villar, J, Giuliani, F, Fenton, TR, et al. INTERGROWTH-21st very preterm size at birth reference charts. Lancet. 2016; 387, 844–845.Google Scholar
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, 1119–1129.CrossRefGoogle ScholarPubMed
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, 2831–2837.Google Scholar
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, 357–363.Google Scholar
14. Chaiworapongsa, T, Chaemsaithong, P, Yeo, L, Romero, R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014; 10, 466–480.Google Scholar
15. Adams Waldorf, KM, McAdams, RM. Influence of infection during pregnancy on fetal development. Reproduction. 2013; 146, R151–R162.Google Scholar
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, 856–862.Google Scholar
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, 456–462.Google Scholar
18. Maruyama, H, Shinozuka, M, Kondoh, Y, et al. Thrombocytopenia in preterm infants with intrauterine growth restriction. Acta Med Okayama. 2008; 62, 313–317.Google ScholarPubMed
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, 512–527.CrossRefGoogle Scholar
20. Malik, S, Cleves, MA, Zhao, W, et al. Association between congenital heart defects and small for gestational age. Pediatrics. 2007; 119, e976–e982.CrossRefGoogle ScholarPubMed
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, 1675–1680.Google Scholar
22. Li, J, Tsuprykov, O, Yang, X, Hocher, B. Paternal programming of offspring cardiometabolic diseases in later life. J Hypertens. 2016; 34, 2111–2126.Google Scholar
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, 105–112.Google Scholar
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, 111–116.Google Scholar
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), 121–124.Google Scholar
26. Martin, H, Lindblad, B, Norman, M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007; 119, 1152–1158.CrossRefGoogle ScholarPubMed
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, 22–27.Google Scholar
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, 2233–2238.Google Scholar
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, 600–606.Google Scholar
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, 1264–1268.CrossRefGoogle ScholarPubMed
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, 20–28.CrossRefGoogle ScholarPubMed
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, R1060–R1068.CrossRefGoogle Scholar
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, R1580–R1588.CrossRefGoogle ScholarPubMed
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, 83–90.Google Scholar
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, 145–153.Google Scholar
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, 2695–2709.Google Scholar
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, 711–715.Google Scholar
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, 448–451.Google Scholar
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, 607–615.Google Scholar
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, 387–394.Google Scholar
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, 371–377.Google Scholar
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, 1615–1620.Google Scholar
43. Skilton, MR, Evans, N, Griffiths, KA, Harmer, JA, Celermajer, DS. Aortic wall thickness in newborns with intrauterine growth restriction. Lancet. 2005; 365, 1484–1486.Google Scholar
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.Google Scholar
45. Litwin, M, Niemirska, A. Intima-media thickness measurements in children with cardiovascular risk factors. Pediatr Nephrol. 2009; 24, 707–719.Google Scholar
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, 1109–1114.Google Scholar
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 e121–121 e129.Google Scholar
48. Crispi, F, Bijnens, B, Figueras, F, et al. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010; 121, 2427–2436.CrossRefGoogle ScholarPubMed
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, 8–16.Google Scholar
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, 1003–1007.Google Scholar
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, 532–537.CrossRefGoogle ScholarPubMed
52. Barker, DJ. The fetal origins of coronary heart disease. Acta Paediatr Suppl. 1997; 422, 78–82.Google Scholar
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, 564–567.CrossRefGoogle ScholarPubMed
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, 2183–2194.CrossRefGoogle ScholarPubMed
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, 45–48.Google Scholar
56. Griendling, KK, Harrison, DG. Dual role of reactive oxygen species in vascular growth. Circ Res. 1999; 85, 562–563.CrossRefGoogle ScholarPubMed
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, 179–183.Google Scholar
58. Touyz, RM, Schiffrin, EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol. 2004; 122, 339–352.Google Scholar
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, 23317–23321.Google Scholar
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, 1141–1148.Google Scholar
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, 488–495.Google Scholar
62. Tyagi, SC, Simon, SR. Regulation of neutrophil elastase activity by elastin-derived peptide. J Biol Chem. 1993; 268, 16513–16518.Google Scholar
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, 189–205.Google Scholar
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, 2572–2579.Google Scholar
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, 6–11.Google Scholar
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.Google Scholar
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, 889–895.Google Scholar
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, 184–189.Google Scholar
69. Chatterjee, A, Black, SM, Catravas, JD. Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascul Pharmacol. 2008; 49, 134–140.CrossRefGoogle ScholarPubMed
70. Förstermann, U, Münzel, T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006; 113, 1708–1714.Google Scholar
71. Searles, CD. Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression. Am J Physiol Cell Physiol. 2006; 291, C803–C816.Google Scholar
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, 60–68.Google Scholar
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, 1070–1073.Google Scholar
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, 298–304.Google Scholar
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, 165–168.Google Scholar
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, 167–172.CrossRefGoogle ScholarPubMed
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, 768–774.Google Scholar
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, 229–239.Google Scholar
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, 532–541.Google Scholar
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, 407–414.Google Scholar
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, 727–732.Google Scholar
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, 142–146.Google Scholar
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, 540–550.Google Scholar
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, 62–73.Google Scholar
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, 2740–2745.Google Scholar
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, 944–952.CrossRefGoogle ScholarPubMed
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, 83–93.CrossRefGoogle ScholarPubMed
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, 3806–3811.Google Scholar
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, 1311–1315.Google Scholar
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, 4221–4226.CrossRefGoogle ScholarPubMed
91. Karkanaki, A, Vavilis, D, Traianos, A, Kalogiannidis, I, Panidis, D. Hormone therapy and asymmetrical dimethylarginine in postmenopausal women. Hormones (Athens). 2010; 9, 127–135.Google Scholar
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, 753–758.Google Scholar
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, 1557–1564.Google Scholar
94. Griendling, KK, FitzGerald, GA. Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003; 108, 1912–1916.Google Scholar
95. Burton, GJ, Jauniaux, E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2011; 25, 287–299.Google Scholar
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, 49–55.Google Scholar
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, 1471–1475.Google Scholar
98. Webster, RP, Roberts, VH, Myatt, L. Protein nitration in placenta – functional significance. Placenta. 2008; 29, 985–994.Google Scholar
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, H1311–H1319.Google Scholar
100. Santilli, F, D’Ardes, D, Davi, G. Oxidative stress in chronic vascular disease: from prediction to prevention. Vascul Pharmacol. 2015; 74, 23–37.Google Scholar
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, 8–16.Google Scholar
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, 9220–9225.Google Scholar
103. d’Uscio, LV, Santhanam, AV, Katusic, ZS. Erythropoietin prevents endothelial dysfunction in GTP-cyclohydrolase I-deficient hph1 mice. J Cardiovasc Pharmacol. 2014; 64, 514–521.CrossRefGoogle ScholarPubMed
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, H1829–H1836.Google Scholar
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, 1201–1209.Google Scholar
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, 9056–9061.Google Scholar
107. Sydow, K, Munzel, T. ADMA and oxidative stress. Atheroscler Suppl. 2003; 4, 41–51.Google Scholar
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, 552–558.Google Scholar
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, 1297–1304.Google Scholar
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.Google Scholar
111. Asahara, T, Murohara, T, Sullivan, A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275, 964–967.Google Scholar
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, 1801–1809.Google Scholar
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, 6620–6625.Google Scholar
114. Hill, JM, Zalos, G, Halcox, JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348, 593–600.Google Scholar
115. Sipos, PI, Crocker, IP, Hubel, CA, Baker, PN. Endothelial progenitor cells: their potential in the placental vasculature and related complications. Placenta. 2010; 31, 1–10.Google Scholar
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, 1769–1773.Google Scholar
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, 1699–1709.Google Scholar
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, 233–238.Google Scholar
119. Minamino, T, Komuro, I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007; 100, 15–26.Google Scholar
120. Erusalimsky, JD, Fenton, M. Further in vivo evidence that cellular senescence is implicated in vascular pathophysiology. Circulation. 2002; 106, e144; author reply e144.Google Scholar
121. Borradaile, NM, Pickering, JG. NAD(+), sirtuins, and cardiovascular disease. Curr Pharm Des. 2009; 15, 110–117.Google Scholar
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, 571–579.Google Scholar
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, 2116–2126.Google Scholar
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, 805–808.Google Scholar
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, 520–522.Google Scholar
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, 2209–2217.Google Scholar
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, 597–604.CrossRefGoogle ScholarPubMed
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, 1627–1631.Google Scholar
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, 1498–1500.Google Scholar
130. Martyn, CN, Barker, DJ, Jespersen, S, et al. Growth in utero, adult blood pressure, and arterial compliance. Br Heart J. 1995; 73, 116–121.Google Scholar
131. Curhan, GC, Willett, WC, Rimm, EB, et al. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation. 1996; 94, 3246–3250.Google Scholar
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, 935–941.Google Scholar
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, 659–665.Google Scholar
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, 448–452.Google Scholar
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, 187–195.Google Scholar
136. Alexander, BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension. 2003; 41, 457–462.Google Scholar
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, 753–758.Google Scholar
138. Ortiz, LA, Quan, A, Zarzar, F, Weinberg, A, Baum, M. Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension. 2003; 41, 328–334.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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, 137–147.Google Scholar
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, 141–152.Google Scholar
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, R1236–R1245.Google Scholar
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), S193–S195.Google Scholar
145. Miller, MJ, Pinto, A, Mullane, KM. Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension. Hypertension. 1987; 10, 164–170.Google Scholar
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, 905–911.CrossRefGoogle ScholarPubMed
147. Verma, S, Anderson, TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002; 105, 546–549.Google Scholar
148. Ludmer, PL, Selwyn, AP, Shook, TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986; 315, 1046–1051.Google Scholar
149. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341, 938–941.Google Scholar
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, 241–245.Google Scholar
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, 408–419.Google Scholar
152. Eriksson, M, Tibblin, G, Cnattingius, S. Low birthweight and ischaemic heart disease. Lancet. 1994; 343, 731.Google Scholar
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, 244–248.Google Scholar
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, S7–S11.Google Scholar
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, F886–F899.Google Scholar
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, S42–S44.Google Scholar
157. Pedrinelli, R, Giampietro, O, Carmassi, F, et al. Microalbuminuria and endothelial dysfunction in essential hypertension. Lancet. 1994; 344, 14–18.Google Scholar
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, 267–273.Google Scholar
159. Perticone, F, Maio, R, Perticone, M, et al. Endothelial dysfunction and subsequent decline in glomerular filtration rate in hypertensive patients. Circulation. 2010; 122, 379–384.Google Scholar
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, 807–813.Google Scholar
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, 770–773.Google Scholar
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, 248–261.Google Scholar
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, 96–103.Google Scholar
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, 1262–1270.Google Scholar
165. Vehaskari, VM, Aviles, DH, Manning, J. Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59, 238–245.Google Scholar
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, 460–467.Google Scholar
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, 22–26.Google Scholar
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, F1944–F1949.Google Scholar
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, F943–F951.Google Scholar
170. Anderson, S, King, AJ, Brenner, BM. Hyperlipidemia and glomerular sclerosis: an alternative viewpoint. Am J Med. 1989; 87, 34N–38N.Google Scholar
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, 423–429.Google Scholar
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.Google Scholar
173. Verhaar, MC, Stroes, E, Rabelink, TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002; 22, 6–13.Google Scholar
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, 437–443.Google Scholar
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, 1193–1201.Google Scholar
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, 1586–1590.Google Scholar
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, 1003–1008.Google Scholar
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, 1017–1020.Google Scholar
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, 45–50.Google Scholar
180. Torrens, C, Brawley, L, Anthony, FW, et al. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006; 47, 982–987.Google Scholar
181. Stroes, ES, van Faassen, EE, Yo, M, et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res. 2000; 86, 1129–1134.Google Scholar
182. Zingg, JM, Azzi, A. Non-antioxidant activities of vitamin E. Curr Med Chem. 2004; 11, 1113–1133.Google Scholar
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, 1847–1853.Google Scholar
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, 189–197.Google Scholar
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, 262–269.Google Scholar
186. Hovdenak, N, Haram, K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012; 164, 127–132.Google Scholar
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, 2123–2133.Google Scholar
188. Rumbold, A, Ota, E, Nagata, C, Shahrook, S, Crowther, CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015; 29, CD004072.Google Scholar
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, 1796–1806.Google Scholar
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, 1038–1044.Google Scholar
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, 1042–1046.Google Scholar
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, 957–964.Google Scholar
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, 1077–1092.Google Scholar
194. Hardeland, R, Cardinali, DP, Srinivasan, V, et al. Melatonin – a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011; 93, 350–384.Google Scholar
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, 1–9.Google Scholar
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, 211–217.Google Scholar
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, 245–257.Google Scholar
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, 188–198.Google Scholar
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, 33–42.Google Scholar
200. Weekley, LB. Effects of melatonin on isolated pulmonary artery and vein: role of the vascular endothelium. Pulm Pharmacol. 1993; 6, 149–154.Google Scholar
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, 1369–1377.Google Scholar
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, 340–345.Google Scholar
203. Curis, E, Nicolis, I, Moinard, C, et al. Almost all about citrulline in mammals. Amino Acids. 2005; 29, 177–205.Google Scholar
204. Romero, MJ, Platt, DH, Caldwell, RB, Caldwell, RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006; 24, 275–290.Google Scholar
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, 43–52.Google Scholar
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, 12–16.Google Scholar
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.Google Scholar
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.Google Scholar
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, 88–96.Google Scholar
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.CrossRefGoogle ScholarPubMed
211. Wu, G, Bazer, FW, Cudd, TA, et al. Pharmacokinetics and safety of arginine supplementation in animals. J Nutr. 2007; 137, 1673S–1680S.Google Scholar
212. Dastjerdi, MV, Hosseini, S, Bayani, L. Sildenafil citrate and uteroplacental perfusion in fetal growth restriction. J Res Med Sci. 2012; 17, 632–636.Google Scholar
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, 2550–2555.Google Scholar
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, 1242–1248.Google Scholar
215. Herraiz, S, Pellicer, B, Serra, V, et al. Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats. BJOG. 2012; 119, 1394–1402.Google Scholar
216. Refuerzo, JS, Sokol, RJ, Aranda, JV, et al. Sildenafil citrate and fetal outcome in pregnant rats. Fetal Diagn Ther. 2006; 21, 259–263.Google Scholar
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, 68R–75R.Google Scholar
218. Chen, M, Zhang, L. Epigenetic mechanisms in developmental programming of adult disease. Drug Discov Today. 2011; 16, 1007–1018.Google Scholar
219. McKay, JA, Mathers, JC. Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf). 2011; 202, 103–118.Google Scholar
220. Kangaspeska, S, Stride, B, Metivier, R, et al. Transient cyclical methylation of promoter DNA. Nature. 2008; 452, 112–115.Google Scholar
221. Lorenzen, JM, Martino, F, Thum, T. Epigenetic modifications in cardiovascular disease. Basic Res Cardiol. 2012; 107, 245.Google Scholar
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, 1129–1133.Google Scholar
223. Kriaucionis, S, Heintz, N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009; 324, 929–930.Google Scholar
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.Google Scholar
225. Canani, RB, Costanzo, MD, Leone, L, et al. Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev. 2011; 24, 198–205.Google Scholar
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, 548–552.Google Scholar
227. Shruti, K, Shrey, K, Vibha, R. Micro RNAs: tiny sequences with enormous potential. Biochem Biophys Res Commun. 2011; 407, 445–449.Google Scholar
228. Sayed, D, Abdellatif, M. MicroRNAs in development and disease. Physiol Rev. 2011; 91, 827–887.Google Scholar
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, 643–648.Google Scholar
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, 138–143.Google Scholar
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, 245–255.Google Scholar
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, 1164–1173.Google Scholar
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, 2107–2117.Google Scholar