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Fetoplacental Vascular Endothelial Dysfunction as an Early Phenomenon in the Programming of Human Adult Diseases in Subjects Born from Gestational Diabetes Mellitus or Obesity in Pregnancy

DOI: 10.1155/2011/349286

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Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the “endothelial L-arginine/nitric oxide signalling pathway.” Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an “altered metabolic state” leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome. 1. Introduction Pregnancy is a physiological state with a complex anatomical and functional interaction between mother and fetus [1]. When this interaction is not a success, the mother, the fetus, or both exhibit functional impairments. Complications of pregnancy are important causes of maternal mortality, where gestational diabetes mellitus (GDM) and obesity of the mother in pregnancy (OP) are major obstetric pathologies. Fetal-maternal interaction could result in metabolic disturbances leading, for example, to placental and endothelial dysfunction [2, 3]. Endothelial dysfunction is defined as an altered capacity of the endothelium to take up and metabolize the cationic amino acid L-arginine, the substrate for nitric oxide (NO) synthesis via NO synthases (NOS) [4, 5]. Interestingly, it is reported that GDM and OP are pathological conditions associated with altered L-arginine transport and NO synthesis (i.e., the “L-arginine/NO signalling pathway”), probably due to altered uptake and metabolism of adenosine [6, 7], an endogenous nucleoside acting as vasodilator in most vascular beds [8, 9]. These pathophysiological characteristics are considered key in the establishment of a “programmed state” of the developing fetus (i.e., “fetal programming”). This concept refers to the impact of abnormal intrauterine conditions on the development of diseases in adulthood and becomes a key mechanism


[1]  L. Sobrevia and P. Casanello, “Placenta,” in Obstetricia, A. Pérez-Sánchez and E. Donoso-Si?a, Eds., pp. 136–176, Mediterráneo, Santiago, Chile, 2011.
[2]  P. Casanello, C. Escudero, and L. Sobrevia, “Equilibrative nucleoside (ENTs) and cationic amino acid (CATS) transporters: implications in foetal endothelial dysfunction in human pregnancy diseases,” Current Vascular Pharmacology, vol. 5, no. 1, pp. 69–84, 2007.
[3]  L. Myatt, “Review: reactive oxygen and nitrogen species and functional adaptation of the placenta,” Placenta, vol. 31, pp. S66–S69, 2010.
[4]  L. J. Ignarro and C. Napoli, “Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis,” Current Diabetes Reports, vol. 5, no. 1, pp. 17–23, 2005.
[5]  S. Moncada and E. A. Higgs, “The discovery of nitric oxide and its role in vascular biology,” British Journal of Pharmacology, vol. 147, supplement 1, pp. S193–S201, 2006.
[6]  F. Westermeier, C. Puebla, J. L. Vega et al., “Equilibrative nucleoside transporters in fetal endothelial dysfunction in diabetes mellitus and hyperglycaemia,” Current Vascular Pharmacology, vol. 7, no. 4, pp. 435–449, 2009.
[7]  F. Westermeier, C. Salomón, M. González et al., “Insulin restores gestational diabetes mellitus-reduced adenosine transport involving differential expression of insulin receptor isoforms in human umbilical vein endothelium,” Diabetes, vol. 60, no. 6, pp. 1677–1687, 2011.
[8]  M. A. Read, I. M. Leitch, W. B. Giles, A. M. Bisits, A. L. Boura, and W. A. Walters, “U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies,” Journal of Hypertension, vol. 17, no. 3, pp. 389–396, 1999.
[9]  H. K. Eltzschig, “Adenosine: an old drug newly discovered,” Anesthesiology, vol. 111, no. 4, pp. 904–915, 2009.
[10]  D. J. Barker, “Fetal programming of coronary heart disease,” Trends in Endocrinology and Metabolism, vol. 13, no. 9, pp. 364–368, 2002.
[11]  K. L. Thornburg, P. F. O'Tierney, and S. Louey, “Review: the placenta is a programming agent for cardiovascular disease,” Placenta, vol. 31, pp. S54–S59, 2010.
[12]  K. D. Bruce and M. A. Hanson, “The developmental origins, mechanisms, and implications of metabolic syndrome,” Journal of Nutrition, vol. 140, no. 3, pp. 648–652, 2010.
[13]  P. M. Catalano, L. Presley, J. Minium, and S. Hauguel de Mouzon, “Fetuses of obese mothers develop insulin resistance in utero,” Diabetes Care, vol. 32, no. 6, pp. 1076–1080, 2009.
[14]  R. H. Jones and S. E. Ozanne, “Intra-uterine origins of type 2 diabetes,” Archives of Physiology and Biochemistry, vol. 113, no. 1, pp. 25–29, 2007.
[15]  C. L. Wei, W. M. Hon, K. H. Lee, and H. E. Khoo, “Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats,” Liver International, vol. 25, no. 3, pp. 647–656, 2005.
[16]  L. Sobrevia, F. Abarzúa, J. K. Nien et al., “Review: differential placental macrovascular and microvascular endothelial dysfunction in gestational diabetes,” Placenta, vol. 25, pp. S159–S164, 2011.
[17]  C. Escudero and L. Sobrevia, “A hypothesis for preeclampsia: adenosine and inducible nitric oxide synthase in human placental microvascular endothelium,” Placenta, vol. 29, no. 6, pp. 469–483, 2008.
[18]  R. M. Barbosa, C. F. Louren?o, R. M. Santos et al., “Chapter 20 in vivo real-time measurement of nitric oxide in anesthetized rat brain,” Methods in Enzymology, vol. 441, pp. 351–367, 2008.
[19]  S. B. Fox and T. Y. Khong, “Lack of innervation of human umbilical cord. An immunohistological and histochemical study,” Placenta, vol. 11, no. 1, pp. 59–62, 1990.
[20]  J. Deanfield, A. Donald, C. Ferri et al., “Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the working group on endothelin and endothelial factors of the European society of hypertension,” Journal of Hypertension, vol. 23, no. 1, pp. 7–17, 2005.
[21]  A. S. Wierzbicki, P. J. Chowienczyk, J. R. Cockcroft et al., “Cardiovascular risk factors and endothelial dysfunction,” Clinical Science, vol. 107, no. 6, pp. 609–615, 2004.
[22]  D. Versari, E. Daghini, A. Virdis, L. Ghiadoni, and S. Taddei, “Endothelium-dependent contractions and endothelial dysfunction in human hypertension,” British Journal of Pharmacology, vol. 157, no. 4, pp. 527–536, 2009.
[23]  P. Libby, P. M. Ridker, and G. K. Hansson, “Progress and challenges in translating the biology of atherosclerosis,” Nature, vol. 473, no. 7347, pp. 317–325, 2011.
[24]  A. Avogaro, G. P. Fadini, A. Gallo, E. Pagnin, and S. de Kreutzenberg, “Endothelial dysfunction in type 2 diabetes mellitus,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 16, supplement 1, pp. S39–S45, 2006.
[25]  Z. Cheng, X. Yang, and H. Wang, “Hyperhomocysteinemia and endothelial dysfunction,” Current Hypertension Reviews, vol. 5, no. 2, pp. 158–165, 2009.
[26]  T. Nakagawa, K. Tanabe, B. P. Croker et al., “Endothelial dysfunction as a potential contributor in diabetic nephropathy,” Nature Reviews Nephrology, vol. 7, no. 1, pp. 36–44, 2011.
[27]  K. Enomoto, H. Yamabe, K. Toyama et al., “Improvement effect on endothelial function in patients with congestive heart failure treated with cardiac resynchronization therapy,” Journal of Cardiology, vol. 58, no. 1, pp. 69–73, 2011.
[28]  A. A. Ogonowski, W. H. Kaesemeyer, L. Jin, V. Ganapathy, F. H. Leibach, and R. W. Caldwell, “Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production,” American Journal of Physiology, vol. 278, no. 1, pp. C136–C143, 2000.
[29]  E. I. Closs, J. S. Scheld, M. Sharafi, and U. F?rstermann, “Substrate supply for nitric-oxide synthase in macrophages and endothelial cells: role of cationic amino acid transporters,” Molecular Pharmacology, vol. 57, no. 1, pp. 68–74, 2000.
[30]  L. Sobrevia and M. González, “A role for insulin on L-arginine transport in fetal endothelial dysfunction in hyperglycaemia,” Current Vascular Pharmacology, vol. 7, no. 4, pp. 467–474, 2009.
[31]  R. Devés and C. A. Boyd, “Transporters for cationic amino acids in animal cells: discovery, structure, and function,” Physiological Reviews, vol. 78, no. 2, pp. 487–545, 1998.
[32]  G. E. Mann, D. L. Yudilevich, and L. Sobrevia, “Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells,” Physiological Reviews, vol. 83, no. 1, pp. 183–252, 2003.
[33]  M. González, V. Gallardo, N. Rodríguez, et al., “Insulin-stimulated L-arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation,” Journal of Cellular Physiology, vol. 226, no. 11, pp. 2916–2924, 2011.
[34]  F. Verrey, E. I. Closs, C. A. Wagner, M. Palacin, H. Endou, and Y. Kanai, “CATs and HATs: the SLC7 family of amino acid transporters,” Pflügers Archiv European Journal of Physiology, vol. 447, no. 5, pp. 532–542, 2004.
[35]  C. Flores, S. Rojas, C. Aguayo et al., “Rapid stimulation of L-arginine transport by D-glucose involves and nitric oxide in human umbilical vein endothelium,” Circulation Research, vol. 92, no. 1, pp. 64–72, 2003.
[36]  J. F. Dye, S. Vause, T. Johnston et al., “Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells,” The FASEB Journal, vol. 18, no. 1, pp. 125–127, 2004.
[37]  E. Tsitsiou, C. P. Sibley, S. W. D'Souza, O. Catanescu, D. W. Jacobsen, and J. D. Glazier, “Homocysteine transport by systems L, A and y+L across the microvillous plasma membrane of human placenta,” Journal of Physiology, vol. 587, no. 16, pp. 4001–4013, 2009.
[38]  Y. Arancibia-Garavilla, F. Toledo, P. Casanello, and L. Sobrevia, “Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium,” Experimental Physiology, vol. 88, no. 6, pp. 699–710, 2003.
[39]  G. Vásquez, F. Sanhueza, R. Vásquez et al., “Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium,” Journal of Physiology, vol. 560, no. 1, pp. 111–122, 2004.
[40]  M. Pastor-Anglada, B. Dérijard, and F. J. Casado, “Mechanisms implicated in the response of system a to hypertonic stress and amino acid deprivation still can be different,” The Journal of General Physiology, vol. 125, no. 1, pp. 41–42, 2005.
[41]  S. A. Baldwin, P. R. Beal, S. Y. Yao, A. E. King, C. E. Cass, and J. D. Young, “The equilibrative nucleoside transporter family, SLC29,” Pflügers Archiv European Journal of Physiology, vol. 447, no. 5, pp. 735–743, 2004.
[42]  C. Aguayo, J. Casado, M. González et al., “Equilibrative nucleoside transporter 2 is expressed in human umbilical vein endothelium, but is not involved in the inhibition of adenosine transport induced by hyperglycaemia,” Placenta, vol. 26, no. 8-9, pp. 641–653, 2005.
[43]  P. Casanello, A. Torres, F. Sanhueza et al., “Equilibrative nucleoside transporter 1 expression is downregulated by hypoxia in human umbilical vein endothelium,” Circulation Research, vol. 97, no. 1, pp. 16–24, 2005.
[44]  C. Salomón, F. Westermeier, P. Casanello, and L. Sobrevia, “Differential modulation of insulin receptor isoforms expression and NOS activity by insulin in human placenta microvascular endothelial cells from gestational diabetes,” Placenta, vol. 31, 2010.
[45]  K. Engel, M. Zhou, and J. Wang, “Identification and characterization of a novel monoamine transporter in the human brain,” Journal of Biological Chemistry, vol. 279, no. 48, pp. 50042–50049, 2004.
[46]  K. Barnes, H. Dobrzynski, S. Foppolo et al., “Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH,” Circulation Research, vol. 99, no. 5, pp. 510–519, 2006.
[47]  E. Guzmán-Gutiérrez, F. Abarzúa, C. Belmar, et al., “Functional link between adenosine and insulin: a hypothesis for fetoplacental vascular endothelial dysfunction in gestational diabetes,” Current Vascular Pharmacology, vol. 9, no. 6, pp. 750–752, 2011.
[48]  R. San Martín and L. Sobrevia, “Gestational diabetes and the adenosine/L-arginine/nitric oxide (ALANO) pathway in human umbilical vein endothelium,” Placenta, vol. 27, no. 1, pp. 1–10, 2006.
[49]  C. Escudero, P. Casanello, and L. Sobrevia, “Human equilibrative nucleoside transporters 1 and 2 may be differentially modulated by A2B adenosine receptors in placenta microvascular endothelial cells from pre-eclampsia,” Placenta, vol. 29, no. 9, pp. 816–825, 2008.
[50]  J. M. Marshall, “The roles of adenosine and related substances in exercise hyperaemia,” Journal of Physiology, vol. 583, no. 3, pp. 835–845, 2007.
[51]  M. Farías, C. Puebla, F. Westermeier et al., “Nitric oxide reduces SLC29A1 promoter activity and adenosine transport involving transcription factor complex hCHOP-C/EBPα in human umbilical vein endothelial cells from gestational diabetes,” Cardiovascular Research, vol. 86, no. 1, pp. 45–54, 2010.
[52]  A. Pandolfi and N. Di Pietro, “High glucose, nitric oxide, and adenosine: a vicious circle in chronic hyperglycaemia?” Cardiovascular Research, vol. 86, no. 1, pp. 9–11, 2010.
[53]  American Diabetes Association, “Diagnosis and classification of diabetes mellitus,” Diabetes Care, vol. 34, supplement 1, pp. S62–S69, 2011.
[54]  J. L. Nold and M. K. Georgieff, “Infants of diabetic mothers,” Pediatric Clinics of North America, vol. 51, no. 3, pp. 619–637, 2004.
[55]  M. F. Greene and C. G. Solomon, “Gestational diabetes mellitus—time to treat,” New England Journal of Medicine, vol. 352, no. 24, pp. 2544–2546, 2005.
[56]  G. Desoye and S. Hauguel-De Mouzon, “The human placenta in gestational diabetes mellitus: the insulin and cytokine network,” Diabetes Care, vol. 30, supplement 2, pp. S120–S126, 2007.
[57]  L. Leach, “Placental vascular dysfunction in diabetic pregnancies: intimations of fetal cardiovascular disease?” Microcirculation, vol. 18, no. 4, pp. 263–269, 2011.
[58]  R. Figueroa, E. Martinez, R. P. Fayngersh, N. Tejani, K. M. Mohazzab-H, and M. S. Wolin, “Alterations in relaxation to lactate and H2O2 in human placental vessels from gestational diabetic pregnancies,” American Journal of Physiology, vol. 278, no. 3, pp. H706–H713, 2000.
[59]  M. Farías, R. San Martín, C. Puebla et al., “Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes,” Journal of Cellular Physiology, vol. 208, no. 2, pp. 451–460, 2006.
[60]  M. González, C. Flores, J. D. Pearson, P. Casanello, and L. Sobrevia, “Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and -2 and membrane hyperpolarization in human umbilical vein endothelial cells,” Pflügers Archiv European Journal of Physiology, vol. 448, no. 4, pp. 383–394, 2004.
[61]  M. Srinivasan, P. Herrero, J. B. McGill et al., “The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus,” Journal of the American College of Cardiology, vol. 46, no. 1, pp. 42–48, 2005.
[62]  L. Sobrevia, S. M. Jarvis, and D. L. Yudilevich, “Adenosine transport in cultured human umbilical vein endothelial cells is reduced in diabetes,” American Journal of Physiology, vol. 267, no. 1, pp. C39–C47, 1994.
[63]  M. Farías, Intracellular signalling in the reduced expression and activity of the equilibrative nucleoside transporter 1 (hENT1) in human umbilical vein endothelium from gestational diabetes mellitus, Ph.D. thesis, Pontificia Universidad Católica de Chile, 2008.
[64]  L. Sobrevia, C. Puebla, F. Farías, and P. Casanello, “Role of equilibrative nucleoside transporters in fetal endothelial dysfunction in gestational diabetes,” in Membrane Transporters and Receptors in Disease, L. Sobrevia and P. Casanello, Eds., pp. 1–25, Research Signpost, Kerala, India, 2009.
[65]  N. M. Nivillac, K. Wasal, D. F. Villani, Z. Naydenova, W. J. Hanna, and I. R. Coe, “Disrupted plasma membrane localization and loss of function reveal regions of human equilibrative nucleoside transporter 1 involved in structural integrity and activity,” Biochimica et Biophysica Acta, vol. 1788, no. 10, pp. 2326–2334, 2009.
[66]  N. M. Nivillac, J. Bacani, and I. R. Coe, “The life cycle of human equilibrative nucleoside transporter 1: from ER export to degradation,” Experimental Cell Research, vol. 317, no. 11, pp. 1567–1579, 2011.
[67]  Y. Yoneyama, R. Sawa, S. Suzuki et al., “Regulation of plasma adenosine levels in normal pregnancy,” Gynecologic and Obstetric Investigation, vol. 53, no. 2, pp. 71–74, 2002.
[68]  Y. Yoneyama, S. Suzuki, R. Sawa, K. Yoneyama, G. G. Power, and T. Araki, “Increased plasma adenosine concentrations and the severity of preeclampsia,” Obstetrics and Gynecology, vol. 100, no. 6, pp. 1266–1270, 2002.
[69]  M. F. Ethier, V. Chander, and J. G. Dobson Jr., “Adenosine stimulates proliferation of human endothelial cells in culture,” American Journal of Physiology, vol. 265, no. 1, pp. H131–H138, 1993.
[70]  G. Mu?oz, R. San Martín, M. Farías et al., “Insulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium,” Journal of Cellular Physiology, vol. 209, no. 3, pp. 826–835, 2006.
[71]  M. J. Romero, D. H. Platt, H. E. Tawfik et al., “Diabetes-induced coronary vascular dysfunction involves increased arginase activity,” Circulation Research, vol. 102, no. 1, pp. 95–102, 2008.
[72]  S. M. Morris Jr., “Recent advances in arginine metabolism: roles and regulation of the arginases,” British Journal of Pharmacology, vol. 157, no. 6, pp. 922–930, 2009.
[73]  ATP III, “Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report,” Circulation, vol. 106, no. 25, pp. 3143–3421, 2002.
[74]  J. Davignon and P. Ganz, “Role of endothelial dysfunction in atherosclerosis,” Circulation, vol. 109, no. 23, pp. III27–III32, 2004.
[75]  V. L. Roger, A. S. Go, D. M. Lloyd-Jones et al., “Heart disease and stroke statistics-2011 update: a report from the American Heart Association,” Circulation, vol. 123, pp. e18–e209, 2011.
[76]  B. J. Arsenault, S. M. Boekholdt, and J. J. Kastelein, “Lipid parameters for measuring risk of cardiovascular disease,” Nature Reviews Cardiology, vol. 8, no. 4, pp. 197–206, 2011.
[77]  C. M. Boney, A. Verma, R. Tucker, and B. R. Vohr, “Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus,” Pediatrics, vol. 115, no. 3, pp. e290–e296, 2005.
[78]  T. D. Clausen, E. R. Mathiesen, T. Hansen et al., “Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 7, pp. 2464–2470, 2009.
[79]  T. R. Moore, “Fetal exposure to gestational diabetes contributes to subsequent adult metabolic syndrome,” American Journal of Obstetrics and Gynecology, vol. 202, no. 6, pp. 643–649, 2010.
[80]  B. Isomaa, P. Almgren, T. Tuomi et al., “Cardiovascular morbidity and mortality associated with the metabolic syndrome,” Diabetes Care, vol. 24, no. 4, pp. 683–689, 2001.
[81]  G. M. Egeland and S. J. Meltzer, “Following in mother's footsteps? Mother-daughter risks for insulin resistance and cardiovascular disease 15 years after gestational diabetes,” Diabetic Medicine, vol. 27, no. 3, pp. 257–265, 2010.
[82]  J. Pirkola, M. V??r?sm?ki, M. Ala-Korpela et al., “Low-grade, systemic inflammation in adolescents: association with early-life factors, gender, and lifestyle,” American Journal of Epidemiology, vol. 171, no. 1, pp. 72–82, 2010.
[83]  S. Mottillo, K. B. Filion, J. Genest et al., “The metabolic syndrome and cardiovascular risk: a systematic review and meta-analysis,” Journal of the American College of Cardiology, vol. 56, no. 14, pp. 1113–1132, 2010.
[84]  E. A. Reece, “The fetal and maternal consequences of gestational diabetes mellitus,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 23, no. 3, pp. 199–203, 2010.
[85]  A. Basaran, “Pregnancy-induced hyperlipoproteinemia: review of the literature,” Reproductive Sciences, vol. 16, no. 5, pp. 431–437, 2009.
[86]  E. Herrera and H. Ortega-Senovilla, “Disturbances in lipid metabolism in diabetic pregnancy—are these the cause of the problem?” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 24, no. 4, pp. 515–525, 2010.
[87]  N. F. Butte, “Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus,” American Journal of Clinical Nutrition, vol. 71, no. 5, pp. 1256–1261, 2000.
[88]  A. Zawiejska, E. Wender-Ozegowska, J. Brazert, and K. Sodowski, “Components of metabolic syndrome and their impact on fetal growth in women with gestational diabetes mellitus,” Journal of Physiology and Pharmacology, vol. 59, supplement 4, pp. S5–S18, 2008.
[89]  G. H. Son, J. Y. Kwon, Y. H. Kim, and Y. W. Park, “Maternal serum triglycerides as predictive factors for large-for- gestational age newborns in women with gestational diabetes mellitus,” Acta Obstetricia et Gynecologica Scandinavica, vol. 89, no. 5, pp. 700–704, 2010.
[90]  C. J. Nolan, S. F. Riley, M. T. Sheedy, J. E. Walstab, and N. A. Bescher, “Maternal serum triglyceride, glucose tolerance, and neonatal birth weight ratio in pregnancy: a study within a racially heterogeneous population,” Diabetes Care, vol. 18, no. 12, pp. 1550–1556, 1995.
[91]  M. Kitajima, S. Oka, I. Yasuhi, M. Fukuda, Y. Rii, and T. Ishimaru, “Maternal serum triglyceride at 24–32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens,” Obstetrics and Gynecology, vol. 97, no. 5, pp. 776–780, 2001.
[92]  U. M. Schaefer-Graf, K. Graf, I. Kulbacka et al., “Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus,” Diabetes Care, vol. 31, no. 9, pp. 1858–1863, 2008.
[93]  C. Marseille-Tremblay, M. Ethier-Chiasson, J. C. Forest et al., “Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta,” Molecular Reproduction and Development, vol. 75, no. 6, pp. 1054–1062, 2008.
[94]  A. L. Magnusson, I. J. Waterman, M. Wennergren, T. Jansson, and T. L. Powell, “Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 9, pp. 4607–4614, 2004.
[95]  C. M. Scifres, B. Chen, D. M. Nelson, and Y. Sadovsky, “Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 7, pp. E1083–E1091, 2011.
[96]  T. Radaelli, J. Lepercq, A. Varastehpour, S. Basu, P. M. Catalano, and S. Hauguel-De Mouzon, “Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus,” American Journal of Obstetrics and Gynecology, vol. 201, no. 2, pp. 209.e1–209.e10, 2009.
[97]  P. Brizzi, G. Tonolo, F. Esposito et al., “Lipoprotein metabolism during normal pregnancy,” American Journal of Obstetrics and Gynecology, vol. 181, no. 2, pp. 430–434, 1999.
[98]  H. J. Avis, B. A. Hutten, M. T. Twickler et al., “Pregnancy in women suffering from familial hypercholesterolemia: a harmful period for both mother and newborn?” Current Opinion in Lipidology, vol. 20, no. 6, pp. 484–490, 2009.
[99]  A. Montes, C. E. Walden, and R. H. Knopp, “Physiologic and supraphysiologic increases in lipoprotein lipids and apoproteins in late pregnancy and postpartum. Possible markers for the diagnosis of “prelipemia”,” Arteriosclerosis, vol. 4, no. 4, pp. 407–417, 1984.
[100]  C. Napoli, F. P. D'Armiento, F. P. Mancini et al., “Fatty streak formation occurs in human fetal aortas and is greatly enhanced maternal, hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atheroeclerotic lesions,” Journal of Clinical Investigation, vol. 100, no. 11, pp. 2680–2690, 1997.
[101]  C. Napoli, C. K. Glass, J. L. Witztum, R. Deutsch, F. P. D'Armiento, and W. Palinski, “Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study,” The Lancet, vol. 354, no. 9186, pp. 1234–1241, 1999.
[102]  K. P. Battaile and R. D. Steiner, “Smith-Lemli-Opitz syndrome: the first malformation syndrome associated with defective cholesterol synthesis,” Molecular Genetics and Metabolism, vol. 71, no. 1-2, pp. 154–162, 2000.
[103]  C. Wadsack, A. Hammer, S. Levak-Frank et al., “Selective cholesteryl ester uptake from high density lipoprotein by human first trimester and term villous trophoblast cells,” Placenta, vol. 24, no. 2-3, pp. 131–143, 2003.
[104]  K. T. Jenkins, L. S. Merkens, M. R. Tubb et al., “Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome,” Molecular Genetics and Metabolism, vol. 94, no. 2, pp. 240–247, 2008.
[105]  J. Stefulj, U. Panzenboeck, T. Becker et al., “Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1,” Circulation Research, vol. 104, no. 5, pp. 600–608, 2009.
[106]  L. A. Woollett, “Review: transport of maternal cholesterol to the fetal circulation,” Placenta, vol. 32, supplement 2, pp. S218–S221, 2011.
[107]  S. H. Badruddin, R. Lalani, M. Khurshid, A. Molla, R. Qureshi, and M. A. Khan, “Serum cholesterol in neonates and their mothers. A pilot study,” Journal of the Pakistan Medical Association, vol. 40, no. 5, pp. 108–109, 1990.
[108]  A. Liguori, F. P. D'Armiento, A. Palagiano et al., “Effect of gestational hypercholesterolaemia on omental vasoreactivity, placental enzyme activity and transplacental passage of normal and oxidised fatty acids,” An International Journal of Obstetrics and Gynaecology, vol. 114, no. 12, pp. 1547–1556, 2007.
[109]  W. Palinski and C. Napoli, “The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis,” The FASEB Journal, vol. 16, no. 11, pp. 1348–1360, 2002.
[110]  M. R. Skilton, “Intrauterine risk factors for precocious atherosclerosis,” Pediatrics, vol. 121, no. 3, pp. 570–574, 2008.
[111]  C. Napoli, L. O. Lerman, F. de Nigris, M. Gossl, M. L. Balestrieri, and A. Lerman, “Rethinking primary prevention of atherosclerosis-related diseases,” Circulation, vol. 114, no. 23, pp. 2517–2527, 2006.
[112]  C. Napoli and W. Palinski, “Maternal hypercholesterolemia during pregnancy influences the later development of atherosclerosis: clinical and pathogenic implications,” European Heart Journal, vol. 22, no. 1, pp. 4–9, 2001.
[113]  W. Palinski, E. Nicolaides, A. Liguori, and C. Napoli, “Influence of maternal dysmetabolic conditions during pregnancy on cardiovascular disease,” Journal of Cardiovascular Translational Research, vol. 2, no. 3, pp. 277–285, 2009.
[114]  C. Napoli and F. Cacciatore, “Novel pathogenic insights in the primary prevention of cardiovascular disease,” Progress in Cardiovascular Diseases, vol. 51, no. 6, pp. 503–523, 2009.
[115]  A. Liguori, F. P. D'Armiento, A. Palagiano, W. Palinski, and C. Napoli, “Maternal C-reactive protein and developmental programming of atherosclerosis,” American Journal of Obstetrics and Gynecology, vol. 198, no. 3, pp. 281.e1–281.e5, 2008.
[116]  P. A. Stapleton, A. G. Goodwill, M. E. James, R. W. Brock, and J. C. Frisbee, “Hypercholesterolemia and microvascular dysfunction: interventional strategies,” Journal of Inflammation, vol. 7, article 54, 2010.
[117]  J. A. Joles, “Crossing borders: linking environmental and genetic developmental factors,” Microcirculation, vol. 18, no. 4, pp. 298–303, 2011.
[118]  E. Koklu, M. Akcakus, S. Kurtoglu et al., “Aortic intima-media thickness and lipid profile in macrosomic newborns,” European Journal of Pediatrics, vol. 166, no. 4, pp. 333–338, 2007.
[119]  A. Leiva, E. Guzmán-Gutiérrez, F. Abarzúa, P. Casanello, and L. Sobrevia, “Maternal supraphysiological hypercholesterolemia leads to reduced endothelium-dependent vasodilation of umbilical vein and increased L-arginine transport in HUVEC,” Journal of Developmental Origins of Health and Disease, vol. 2, supplement 1, p. S95, 2011.
[120]  M. González, E. Mu?oz, C. Puebla, et al., “Maternal and fetal metabolic dysfunction in pregnancy diseases associated with vascular oxidative and nitrative stress,” in The Molecular Basis for Origin of Fetal Congenital Abnormalities and Maternal Health: An overview of Association with Oxidative Stress, B. M. Matata and M. Elahi, Eds., Bentham, USA, 2011.
[121]  Y. Aggoun, I. Szezepanski, and D. Bonnet, “Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children,” Pediatric Research, vol. 58, no. 2, pp. 173–178, 2005.
[122]  S. Riggio, G. Mandraffino, M. A. Sardo et al., “Pulse wave velocity and augmentation index, but not intima-media thickness, are early indicators of vascular damage in hypercholesterolemic children,” European Journal of Clinical Investigation, vol. 40, no. 3, pp. 250–257, 2010.
[123]  M. A. Creager, J. P. Cooke, M. E. Mendelsohn et al., “Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans,” Journal of Clinical Investigation, vol. 86, no. 1, pp. 228–234, 1990.
[124]  K. Egashira, T. Inou, Y. Hirooka et al., “Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions,” Journal of Clinical Investigation, vol. 91, no. 1, pp. 29–37, 1993.
[125]  T. Münzel, C. Sinning, F. Post, A. Warnholtz, and E. Schulz, “Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction,” Annals of Medicine, vol. 40, no. 3, pp. 180–196, 2008.
[126]  S. Kawashima and M. Yokoyama, “Dysfunction of endothelial nitric oxide synthase and atherosclerosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 6, pp. 998–1005, 2004.
[127]  I. F. Schwartz, M. Ingbir, T. Chernichovski et al., “Arginine uptake is attenuated, through post-translational regulation of cationic amino acid transporter-1, in hyperlipidemic rats,” Atherosclerosis, vol. 194, no. 2, pp. 357–363, 2007.
[128]  W. Z. Zhang, K. Venardos, S. Finch, and D. M. Kaye, “Detrimental effect of oxidized LDL on endothelial arginine metabolism and transportation,” International Journal of Biochemistry and Cell Biology, vol. 40, pp. 920–928, 2008.
[129]  J. K. Liao, W. S. Shin, W. Y. Lee, and S. L. Clark, “Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase,” Journal of Biological Chemistry, vol. 270, no. 1, pp. 319–324, 1995.
[130]  F. Vidal, C. Colomé, J. Martínez-González, and L. Badimon, “Atherogenic concentrations of native low-density lipoproteins down- regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells,” European Journal of Biochemistry, vol. 252, no. 3, pp. 378–384, 1998.
[131]  A. Jiménez, M. M. Arriero, A. López-Blaya et al., “Regulation of endothelial nitric oxide synthase expression in the vascular wall and in mononuclear cells from hypercholesterolemic rabbits,” Circulation, vol. 104, no. 15, pp. 1822–1830, 2001.
[132]  M. Ozaki, S. Kawashima, T. Yamashita et al., “Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice,” Journal of Clinical Investigation, vol. 110, no. 3, pp. 331–340, 2002.
[133]  F. T. Tang, Z. Y. Qian, P. Q. Liu et al., “Crocetin improves endothelium-dependent relaxation of thoracic aorta in hypercholesterolemic rabbit by increasing eNOS activity,” Biochemical Pharmacology, vol. 72, no. 5, pp. 558–565, 2006.
[134]  J. Dulak, M. Polus, I. Guevara, A. Polus, J. Hartwich, and A. Dembińska-Kie?, “Regulation of inducible nitric oxide synthase (iNOS) and GTP cyclohydrolase I (GTP-CH I) gene expression by OX-LDL in rat vascular smooth muscle cells,” Journal of Physiology and Pharmacology, vol. 48, no. 4, pp. 689–697, 1997.
[135]  J. Dulak, M. Polus, I. Guevara et al., “Oxidized low density lipoprotein inhibits inducible nitric oxide synthase, GTP cyclohydrolase I and transforming growth factor beta gene expression in rat macrophages,” Journal of Physiology and Pharmacology, vol. 50, no. 3, pp. 429–441, 1999.
[136]  S. Ryoo, C. A. Lemmon, K. G. Soucy et al., “Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signaling,” Circulation Research, vol. 99, no. 9, pp. 951–960, 2006.
[137]  S. Ryoo, G. Gupta, A. Benjo et al., “Endothelial arginase II: a novel target for the treatment of atherosclerosis,” Circulation Research, vol. 102, no. 8, pp. 923–932, 2008.
[138]  S. Ryoo, A. Bhunia, F. Chang, A. Shoukas, D. E. Berkowitz, and L. H. Romer, “OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling,” Atherosclerosis, vol. 214, no. 2, pp. 279–287, 2011.
[139]  D. Spruijt-Metz, “Etiology, treatment, and prevention of obesity in childhood and adolescence: a decade in review,” Journal of Research on Adolescence, vol. 21, no. 1, pp. 129–152, 2011.
[140]  S. E. Shoelson, L. Herrero, and A. Naaz, “Obesity, Inflammation, and Insulin Resistance,” Gastroenterology, vol. 132, no. 6, pp. 2169–2180, 2007.
[141]  S. Nishimura, I. Manabe, and R. Nagai, “Adipose tissue inflammation in obesity and metabolic syndrome,” Discovery Medicine, vol. 8, no. 41, pp. 55–60, 2009.
[142]  M. Tesauro and C. Cardillo, “Obesity, blood vessels and metabolic syndrome,” Acta Physiologica, vol. 203, no. 1, pp. 279–286, 2011.
[143]  World Health Organization, “Obesity and Overweight,” Fact Sheet 11, March 2011.
[144]  A. A. Hedley, C. L. Ogden, C. L. Johnson, M. D. Carroll, L. R. Curtin, and K. M. Flegal, “Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002,” Journal of the American Medical Association, vol. 291, no. 23, pp. 2847–2850, 2004.
[145]  A. M. Magarey, L. A. Daniels, T. J. Boulton, and R. A. Cockington, “Predicting obesity in early adulthood from childhood and parental obesity,” International Journal of Obesity, vol. 27, no. 4, pp. 505–513, 2003.
[146]  S. Danielzik, M. Czerwinski-Mast, K. Langn?se, B. Dilba, and M. J. Müller, “Parental overweight, socioeconomic status and high birth weight are the major determinants of overweight and obesity in 5-7 y-old children: baseline data of the Kiel Obesity Prevention Study (KOPS),” International Journal of Obesity, vol. 28, no. 11, pp. 1494–1502, 2004.
[147]  P. J. Salsberry and P. B. Reagan, “Dynamics of early childhood overweight,” Pediatrics, vol. 116, no. 6, pp. 1329–1338, 2005.
[148]  H. M. Ehrenberg, C. P. Durnwald, P. Catalano, and B. M. Mercer, “The influence of obesity and diabetes on the risk of cesarean delivery,” American Journal of Obstetrics and Gynecology, vol. 191, no. 3, pp. 969–974, 2004.
[149]  B. Rosenn, “Obesity and diabetes: a recipe for obstetric complications,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 21, no. 3, pp. 159–164, 2008.
[150]  J. M. Salbaum and C. Kappen, “Diabetic embryopathy: a role for the epigenome?” Birth Defects Research Part A, vol. 91, no. 8, pp. 770–780, 2011.
[151]  V. O'Dwyer, N. Farah, C. Fattah, N. O'Connor, M. M. Kennelly, and M. J. Turner, “The risk of caesarean section in obese women analysed by parity,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 158, no. 1, pp. 28–32, 2011.
[152]  J. C. Challier, S. Basu, T. Bintein et al., “Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta,” Placenta, vol. 29, no. 3, pp. 274–281, 2008.
[153]  K. A. Roberts, S. C. Riley, R. M. Reynolds et al., “Placental structure and inflammation in pregnancies associated with obesity,” Placenta, vol. 32, no. 3, pp. 247–254, 2011.
[154]  L. Higgins, S. L. Greenwood, M. Wareing, C. P. Sibley, and T. A. Mills, “Obesity and the placenta: a consideration of nutrient exchange mechanisms in relation to aberrant fetal growth,” Placenta, vol. 32, no. 1, pp. 1–7, 2011.
[155]  U. Hiden, I. Lang, N. Ghaffari-Tabrizi, M. Gauster, U. Lang, and G. Desoye, “Insulin action on the human placental endothelium in normal and diabetic pregnancy,” Current Vascular Pharmacology, vol. 7, no. 4, pp. 460–466, 2009.
[156]  T. Becker, M. J. Vermeulen, P. R. Wyatt, C. Meier, and J. G. Ray, “Maternal obesity and the risk of placental vascular disease,” Journal of Obstetrics and Gynaecology Canada, vol. 30, no. 12, pp. 1132–1136, 2008.
[157]  F. C. Denison, J. Price, C. Graham, S. Wild, and W. A. Liston, “Maternal obesity, length of gestation, risk of postdates pregnancy and spontaneous onset of labour at term,” An International Journal of Obstetrics and Gynaecology, vol. 115, no. 6, pp. 720–725, 2008.
[158]  S. Y. Chu, W. M. Callaghan, S. Y. Kim et al., “Maternal obesity and risk of gestational diabetes mellitus,” Diabetes Care, vol. 30, no. 8, pp. 2070–2076, 2007.
[159]  J. Lepercq, M. Cauzac, N. Lahlou et al., “Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin,” Diabetes, vol. 47, no. 5, pp. 847–850, 1998.
[160]  M. A. Williams, P. J. Havel, M. W. Schwartz et al., “Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women,” Paediatric and Perinatal Epidemiology, vol. 13, no. 2, pp. 190–204, 1999.
[161]  T. Reimer, D. Koczan, B. Gerber, D. Richter, H. J. Thiesen, and K. Friese, “Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes,” Molecular Human Reproduction, vol. 8, no. 7, pp. 674–680, 2002.
[162]  P. A. Kern, S. Ranganathan, C. Li, L. Wood, and G. Ranganathan, “Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance,” American Journal of Physiology, vol. 280, no. 5, pp. E745–E751, 2001.
[163]  A. D. Pradhan, J. E. Manson, N. Rifai, J. E. Buring, and P. M. Ridker, “C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus,” Journal of the American Medical Association, vol. 286, no. 3, pp. 327–334, 2001.
[164]  B. Vozarova, C. Weyer, K. Hanson, P. A. Tataranni, C. Bogardus, and R. E. Pratley, “Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion,” Obesity Research, vol. 9, no. 7, pp. 414–417, 2001.
[165]  P. Dandona, R. Weinstock, K. Thusu, E. Abdel-Rahman, A. Aljada, and T. Wadden, “Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 8, pp. 2907–2910, 1998.
[166]  P. Dandona, A. Aljada, and A. Bandyopadhyay, “Inflammation: the link between insulin resistance, obesity and diabetes,” Trends in Immunology, vol. 25, no. 1, pp. 4–7, 2004.
[167]  S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante Jr., “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003.
[168]  G. Fantuzzi, “Adipose tissue, adipokines, and inflammation,” Journal of Allergy and Clinical Immunology, vol. 115, no. 5, pp. 911–920, 2005.
[169]  H. Tilg and A. R. Moschen, “Adipocytokines: mediators linking adipose tissue, inflammation and immunity,” Nature Reviews Immunology, vol. 6, no. 10, pp. 772–783, 2006.
[170]  K. Meijer, M. de Vries, S. Al-Lahham et al., “Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages,” PLoS One, vol. 6, no. 3, Article ID e17154, 2011.
[171]  J. A. Suwaidi, S. Hamasaki, S. T. Higano, R. A. Nishimura, D. R. Holmes, and A. Lerman, “Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction,” Circulation, vol. 101, no. 9, pp. 948–954, 2000.
[172]  F. Kim, M. Pham, E. Maloney et al., “Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 11, pp. 1982–1988, 2008.
[173]  E. Yamamoto, T. Nakamura, K. Kataoka et al., “Nifedipine prevents vascular endothelial dysfunction in a mouse model of obesity and type 2 diabetes, by improving eNOS dysfunction and dephosphorylation,” Biochemical and Biophysical Research Communications, vol. 403, no. 3-4, pp. 258–263, 2010.
[174]  T. B. Nascimento, R. D. Baptista, P. C. Pereira, et al., “Vascular alterations in high-fat diet-obese rats: role of Endothelial L-arginine/NO Pathway,” Arquivos Brasileiros de Cardiologia, vol. 97, no. 1, pp. 40–45, 2011.
[175]  M. J. Zhu, M. Du, P. W. Nathanielsz, and S. P. Ford, “Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta,” Placenta, vol. 31, no. 5, pp. 387–391, 2010.
[176]  P. Singla, A. Bardoloi, and A. A. Parkash, “Metabolic effects of obesity: a review,” World Journal of Diabetes, vol. 1, pp. 76–88, 2010.
[177]  F. von Versen-H?ynck, A. Rajakumar, M. S. Parrott, and R. W. Powers, “Leptin affects system a amino acid transport activity in the human placenta: evidence for STAT3 dependent mechanisms,” Placenta, vol. 30, no. 4, pp. 361–367, 2009.
[178]  D. M. Farley, J. Choi, D. J. Dudley et al., “Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity,” Placenta, vol. 31, no. 8, pp. 718–724, 2010.
[179]  K. Fujita, K. Wada, Y. Nozaki et al., “Serum nitric oxide metabolite as a biomarker of visceral fat accumulation: clinical significance of measurement for nitrate/nitrite,” Medical Science Monitor, vol. 17, no. 3, pp. 123–131, 2011.
[180]  L. Rong-Na, Z. Xiang-Jun, C. Yu-Han, L. Ling-Qiao, and H. Gang, “Interaction between hydrogen sulfide and nitric oxide on cardiac protection in rats with metabolic syndrome,” Zhongguo Yi Xue Ke Xue Yuan Xue Bao, vol. 33, no. 1, pp. 25–32, 2011.
[181]  R. S. Miller, D. Diaczok, and D. W. Cooke, “Repression of GLUT4 expression by the endoplasmic reticulum stress response in 3T3-L1 adipocytes,” Biochemical and Biophysical Research Communications, vol. 362, no. 1, pp. 188–192, 2007.
[182]  N. Shen, X. Yu, F. Y. Pan, X. Gao, B. Xue, and C. J. Li, “An early response transcription factor, Egr-1, enhances insulin resistance in type 2 diabetes with chronic hyperinsulinism,” Journal of Biological Chemistry, vol. 286, no. 16, pp. 14508–14515, 2011.
[183]  P. M. Catalano, “Obesity and pregnancy—the propagation of a viscous cycle?” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 8, pp. 3505–3506, 2003.
[184]  G. C. Curhan, W. C. Willett, E. B. Rimm, D. Spiegelman, A. L. Ascherio, and M. J. Stampfer, “Birth weight and adult hypertension, diabetes mellitus, and obesity in US men,” Circulation, vol. 94, no. 12, pp. 3246–3250, 1996.
[185]  E. Oken, S. L. Rifas-Shiman, A. E. Field, A. L. Frazier, and M. W. Gillman, “Maternal gestational weight gain and offspring weight in adolescence,” Obstetrics and Gynecology, vol. 112, no. 5, pp. 999–1006, 2008.
[186]  B. H. Wrotniak, J. Shults, S. Butts, and N. Stettler, “Gestational weight gain and risk of overweight in the offspring at age 7 y in a multicenter, multiethnic cohort study,” American Journal of Clinical Nutrition, vol. 87, no. 6, pp. 1818–1824, 2008.
[187]  E. Oken, E. M. Taveras, K. P. Kleinman, J. W. Rich-Edwards, and M. W. Gillman, “Gestational weight gain and child adiposity at age 3 years,” American Journal of Obstetrics and Gynecology, vol. 196, no. 4, pp. 322.e1–322.e8, 2007.
[188]  E. Oken and M. W. Gillman, “Fetal origins of obesity,” Obesity Research, vol. 11, no. 4, pp. 496–506, 2003.
[189]  G. Dorner and A. Plagemann, “Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life,” Hormone and Metabolic Research, vol. 26, no. 5, pp. 213–221, 1994.
[190]  A. Fraser, K. Tilling, C. MacDonald-Wallis et al., “Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood,” Circulation, vol. 121, no. 23, pp. 2557–2564, 2010.
[191]  B. M. Margetts, M. G. Rowland, F. A. Foord, A. M. Cruddas, T. J. Cole, and D. J. Barker, “The relation of maternal weight to the blood pressures of Gambian children,” International Journal of Epidemiology, vol. 20, no. 4, pp. 938–943, 1991.
[192]  K. M. Godfrey, T. Forrester, D. J. Barker et al., “Maternal nutritional status in pregnancy and blood pressure in childhood,” British Journal of Obstetrics and Gynaecology, vol. 101, no. 5, pp. 398–403, 1994.
[193]  A. Laor, D. K. Stevenson, J. Shemer, R. Gale, and D. S. Seidman, “Size at birth, maternal nutritional status in pregnancy, and blood pressure at age 17: population based analysis,” British Medical Journal, vol. 315, no. 7106, pp. 449–453, 1997.
[194]  P. M. Clark, C. Atton, C. M. Law, A. Shiell, K. Godfrey, and D. J. Barker, “Weight gain in pregnancy, triceps skinfold thickness, and blood pressure, in offspring,” Obstetrics and Gynecology, vol. 91, no. 1, pp. 103–107, 1998.
[195]  A. A. Mamun, M. O'Callaghan, L. Callaway, G. Williams, J. Najman, and D. A. Lawlor, “Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of ageevidence from a birth cohort study,” Circulation, vol. 119, no. 13, pp. 1720–1727, 2009.
[196]  M. F. Sewell, L. Huston-Presley, D. M. Super, and P. Catalano, “Increased neonatal fat mass, not lean body mass, is associated with maternal obesity,” American Journal of Obstetrics and Gynecology, vol. 195, no. 4, pp. 1100–1103, 2006.
[197]  B. E. Metzger, B. L. Silverman, N. Freinkel, S. L. Dooley, E. S. Ogata, and O. C. Green, “Amniotic fluid insulin concentration as a predictor of obesity,” Archives of Disease in Childhood, vol. 65, no. 10, pp. 1050–1052, 1990.
[198]  M. W. Gillman, S. Rifas-Shiman, C. S. Berkey, A. E. Field, and G. A. Colditz, “Maternal gestational diabetes, birth weight, and adolescent obesity,” Pediatrics, vol. 111, no. 3, pp. 221–226, 2003.
[199]  D. Dabelea, “The predisposition to obesity and diabetes in offspring of diabetic mothers,” Diabetes Care, vol. 30, supplement 2, pp. S169–S174, 2007.
[200]  D. Dabelea, R. L. Hanson, P. H. Bennett, J. Roumain, W. C. Knowler, and D. J. Pettitt, “Increasing prevalence of type II diabetes in American Indian children,” Diabetologia, vol. 41, no. 8, pp. 904–910, 1998.
[201]  D. Dabelea, W. C. Knowler, and D. J. Pettitt, “Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 9, no. 1, pp. 83–88, 2000.
[202]  T. D. Clausen, E. R. Mathiesen, T. Hansen et al., “High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia,” Diabetes Care, vol. 31, no. 2, pp. 340–346, 2008.
[203]  D. J. Pettitt and W. C. Knowler, “Long-term effects of the intrauterine environment, birth weight, and breast-feeding in Pima Indians,” Diabetes Care, vol. 21, supplement 2, pp. B138–B141, 1998.
[204]  Y. Yogev and G. H. Visser, “Obesity, gestational diabetes and pregnancy outcome,” Seminars in Fetal and Neonatal Medicine, vol. 14, no. 2, pp. 77–84, 2009.
[205]  L. Schack-Nielsen, K. F. Michaelsen, M. Gamborg, E. L. Mortensen, and T. I. S?rensen, “Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood,” International Journal of Obesity, vol. 34, no. 1, pp. 67–74, 2010.
[206]  J. A. Armitage, L. Poston, and P. D. Taylor, “Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity,” Frontiers of Hormone Research, vol. 36, pp. 73–84, 2008.
[207]  T. A. Hillier, K. L. Pedula, M. M. Schmidt, J. A. Mullen, M. A. Charles, and D. J. Pettitt, “Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia,” Diabetes Care, vol. 30, no. 9, pp. 2287–2292, 2007.
[208]  M. W. Gillman, H. Oakey, P. A. Baghurst, R. E. Volkmer, J. S. Robinson, and C. A. Crowther, “Effect of treatment of gestational diabetes mellitus on obesity in the next generation,” Diabetes Care, vol. 33, no. 5, pp. 964–968, 2010.
[209]  I. Rogers, “The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life,” International Journal of Obesity, vol. 27, no. 7, pp. 755–777, 2003.
[210]  M. A. Charles, D. J. Pettitt, R. L. Hanson et al., “Familial and metabolic factors related to blood pressure in Pima Indian children,” American Journal of Epidemiology, vol. 140, no. 2, pp. 123–131, 1994.
[211]  C. S. Wright, S. L. Rifas-Shiman, J. W. Rich-Edwards, E. M. Taveras, M. W. Gillman, and E. Oken, “Intrauterine exposure to gestational diabetes, child adiposity, and blood pressure,” American Journal of Hypertension, vol. 22, no. 2, pp. 215–220, 2009.
[212]  E. P. Gunderson, C. P. Quesenberry, D. R. Jacobs, J. Feng, C. E. Lewis, and S. Sidney, “Longitudinal study of prepregnancy cardiometabolic risk factors and subsequent risk of gestational diabetes mellitus: the CARDIA study,” American Journal of Epidemiology, vol. 172, no. 10, pp. 1131–1143, 2010.
[213]  C. R. Assump??o, T. M. Brunini, N. R. Pereira et al., “Insulin resistance in obesity and metabolic syndrome: is there a connection with platelet l-arginine transport?” Blood Cells, Molecules, and Diseases, vol. 45, no. 4, pp. 338–342, 2010.
[214]  K. Kikuta, T. Sawamura, S. Miwa, N. Hashimoto, and T. Masaki, “High-affinity arginine transport of bovine aortic endothelial cells is impaired by lysophosphatidylcholine,” Circulation Research, vol. 83, no. 11, pp. 1088–1096, 1998.
[215]  K. Posch, S. Simecek, T. C. Wascher et al., “Glycated low-density lipoprotein attenuates shear stress-induced nitric oxide synthesis by inhibition of shear stress-activated L-arginine uptake in endothelial cells,” Diabetes, vol. 48, no. 6, pp. 1331–1337, 1999.
[216]  M. T. Jay, S. Chirico, R. C. Siow et al., “Modulation of vascular tone by low density lipoproteins: effects on L-arginine transport and nitric oxide synthesis,” Experimental Physiology, vol. 82, no. 2, pp. 349–360, 1997.
[217]  A. Nuszkowski, R. Gr?bner, G. Marsche, A. Unbehaun, E. Malle, and R. Heller, “Hypochlorite-modified low density lipoprotein inhibits nitric oxide synthesis in endothelial cells via an intracellular dislocalization of endothelial nitric-oxide synthase,” Journal of Biological Chemistry, vol. 276, no. 17, pp. 14212–14221, 2001.
[218]  W. G. Rossmanith, U. Hoffmeister, S. Wolfahrt et al., “Expression and functional analysis of endothelial nitric oxide synthase (eNOS) in human placenta,” Molecular Human Reproduction, vol. 5, no. 5, pp. 487–494, 1999.
[219]  J. Ketonen, T. Pilvi, and E. Mervaala, “Caloric restriction reverses high-fat diet-induced endothelial dysfunction and vascular superoxide production in C57Bl/6 mice,” Heart and Vessels, vol. 25, no. 3, pp. 254–262, 2010.
[220]  S. Kagota, E. Chia, and J. J. McGuire, “Preserved arterial vasodilation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice,” British Journal of Pharmacology, vol. 164, no. 2, pp. 358–371, 2011.
[221]  S. Fatani, I. Itua, P. Clark, C. Wong, and E. K. Naderali, “The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage,” International Journal of General Medicine, vol. 4, pp. 211–219, 2011.
[222]  J. L. Di Iulio, N. M. Gude, R. G. King, C. G. Li, M. J. Rand, and S. P. Brennecke, “Human placental nitric oxide synthase activity is not altered in diabetes,” Clinical Science, vol. 97, no. 1, pp. 123–128, 1999.
[223]  H. B. Eccleston, K. K. Andringa, A. M. Betancourt et al., “Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice,” Antioxidants and Redox Signaling, vol. 15, no. 2, pp. 447–459, 2011.
[224]  P. M. Catalano and S. Hauguel-De Mouzon, “Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic?” American Journal of Obstetrics and Gynecology, vol. 204, no. 6, pp. 479–487, 2011.
[225]  J. Pedersen, Diabetes and pregnancy: blood sugar of newborn infants, Ph.D. thesis, Danish Science Press, Copenhagen, Denmark, 1952.
[226]  T. W. Leung and T. T. Lao, “Placental size and large-for-gestational-age infants in women with abnormal glucose tolerance in pregnancy,” Diabetic Medicine, vol. 17, no. 1, pp. 48–52, 2000.
[227]  S. Hauguel-de Mouzon, J. Lepercq, and P. Catalano, “The known and unknown of leptin in pregnancy,” American Journal of Obstetrics and Gynecology, vol. 194, no. 6, pp. 1537–1545, 2006.
[228]  J. T. Smith and B. J. Waddell, “Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids,” Endocrinology, vol. 144, no. 7, pp. 3024–3030, 2003.
[229]  F. M. Stewart, D. J. Freeman, J. E. Ramsay, I. A. Greer, M. Caslake, and W. R. Ferrell, “Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 3, pp. 969–975, 2007.
[230]  D. J. Tuffnell, J. West, and S. A. Walkinshaw, “Treatments for gestational diabetes and impaired glucose tolerance in pregnancy,” Cochrane Database of Systematic Reviews, no. 3, Article ID CD003395, 2003.
[231]  C. A. Crowther, J. E. Hiller, J. R. Moss, A. J. McPhee, W. S. Jeffries, and J. S. Robinson, “Effect of treatment of gestational diabetes mellitus on pregnancy outcomes,” New England Journal of Medicine, vol. 352, no. 24, pp. 2477–2486, 2005.
[232]  A. Burguet, “Long term outcome in children of mothers with gestational diabetes,” Journal de Gynecologie Obstetrique et Biologie de la Reproduction, vol. 39, no. 8, supplement 2, pp. S322–S337, 2010.


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