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Research Article

The anti-aging factor α-klotho during human pregnancy and its expression in pregnancies complicated by small-for-gestational-age neonates and/or preeclampsia

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Pages 449-457 | Received 17 Apr 2013, Accepted 19 Jun 2013, Published online: 19 Aug 2013

References

  • Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390:45–51
  • Kawaguchi H, Manabe N, Miyaura C, et al. Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J Clin Invest 1999;104:229–37
  • Tsujikawa H, Kurotaki Y, Fujimori T, et al. A gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol 2003;17:2393–403
  • Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science 2005;309:1829–33
  • Kuro-o M. Klotho. Pflugers Arch 2010;459:333–43
  • Matsumura Y, Aizawa H, Shiraki-Iida T, et al. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998;242:626–30
  • Aizawa H, Saito Y, Nakamura T, et al. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun 1998;249:865–71
  • Imura A, Iwano A, Tohyama O, et al. Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett 2004;565:143–7
  • Wang Y, Sun Z. Current understanding of klotho. Ageing Res Rev 2009;8:43–51
  • Kuro-o M. Klotho in health and disease. Curr Opin Nephrol Hypertens 2012;21:362–8
  • Nabeshima Y, Imura H. alpha-Klotho: a regulator that integrates calcium homeostasis. Am J Nephrol 2008;28:455–64
  • Imura A, Tsuji Y, Murata M, et al. alpha-Klotho as a regulator of calcium homeostasis. Science 2007;316:1615–18
  • Huang CL, Moe OW. Klotho: a novel regulator of calcium and phosphorus homeostasis. Pflugers Arch 2011;462:185–93
  • Kuro-o M. Overview of the FGF23-Klotho axis. Pediatr Nephrol 2010;25:583–90
  • Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 2009;5:611–19
  • Shimada T, Takeshita Y, Murohara T, et al. Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse. Circulation 2004;110:1148–55
  • Fukino K, Suzuki T, Saito Y, et al. Regulation of angiogenesis by the aging suppressor gene klotho. Biochem Biophys Res Commun 2002;293:332–7
  • Mori K, Yahata K, Mukoyama M, et al. Disruption of klotho gene causes an abnormal energy homeostasis in mice. Biochem Biophys Res Commun 2000;278:665–70
  • Razzaque MS. The role of Klotho in energy metabolism. Nat Rev Endocrinol 2012;8:579–87
  • Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chin Med J (Engl) 2004;117:742–7
  • Saito Y, Yamagishi T, Nakamura T, et al. Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun 1998;248:324–9
  • Kuro-o M. Klotho as a regulator of oxidative stress and senescence. Biol Chem 2008;389:233–41
  • Yamamoto M, Clark JD, Pastor JV, et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 2005;280:38029–34
  • Semba RD, Cappola AR, Sun K, et al. Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc 2011;59:1596–601
  • Romero R. Prenatal medicine: the child is the father of the man. 1996. J Matern Fetal Neona 2009;22:636–9
  • Di Renzo GC. The great obstetrical syndromes. J Matern Fetal Neona 2009;22:633–5
  • Brosens I, Pijnenborg R, Vercruysse L, Romero R. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol 2011;204:193–201
  • Romero R, Lockwood C, Oyarzun E, Hobbins JC. Toxemia: new concepts in an old disease. Semin Perinatol 1988;12:302–23
  • Xiao R, Sorensen TK, Williams MA, Luthy DA. Influence of pre-eclampsia on fetal growth. J Matern Fetal Neona 2003;13:157–62
  • Villar J, Carroli G, Wojdyla D, et al. Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions? Am J Obstet Gynecol 2006;194:921–31
  • van Eerd EA, Roex AJ, Nikpoor P, Dekker GA. Adverse perinatal outcome and maternal risk factors in population versus customized defined SGA babies. J Matern Fetal Neona 2012;25:369–73
  • Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005;308:1592–4
  • Gotsch F, Romero R, Kusanovic JP, et al. Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: soluble Tie-2. J Matern Fetal Neonatal Med 2008;21:389–402
  • Erez O, Romero R, Espinoza J, et al. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med 2008;21:279–87
  • Zhang J, Meikle S, Trumble A. Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertens Pregnancy 2003;22:203–12
  • Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 2008;21:9–23
  • Giapros V, Drougia A, Krallis N, et al. Morbidity and mortality patterns in small-for-gestational age infants born preterm. J Matern Fetal Neona 2012;25:153–7
  • Jelin AC, Cheng YW, Shaffer BL, et al. Early-onset preeclampsia and neonatal outcomes. J Matern Fetal Neona 2010;23:389–92
  • Mirza FG, Strohsnitter WC, Rivera J, Gyamfi-Bannerman C. Intrauterine growth restriction with abnormal umbilical artery Dopplers: a harbinger for preeclampsia? J Matern Fetal Neona 2012;25:2658–61
  • Nanthakomon T, Uerpairojkit B. Outcome of small-for-gestational-age fetuses according to umbilical artery Doppler: is there any yield from additional middle cerebral artery Doppler? J Matern Fetal Neona 2010;23:900–5
  • Jelin AC, Cheng YW, Shaffer BL, et al. Early-onset preeclampsia and neonatal outcomes. J Matern Fetal Neonatal Med 2010;23:389–92
  • Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancy-related mortality in the United States, 1998 to 2005. Obstetrics and gynecology 2010;116:1302–9
  • Schneider S, Freerksen N, Maul H, et al. Risk groups and maternal-neonatal complications of preeclampsia–current results from the national German Perinatal Quality Registry. J Perinat Med 2011;39:257–65
  • Adinma ED. Maternal and perinatal outcome of eclampsia in tertiary health institution in Southeast Nigeria. J Matern Fetal Neonatal Med 2013;26:211–14
  • Cosar H, Ozer E, Topel H, et al. Neuronal apoptosis in the neonates born to preeclamptic mothers. J Matern Fetal Neonatal Med 2013;26:1143--6
  • Samuel A, Lin C, Parviainen K, Jeyabalan A. Expectant management of preeclampsia superimposed on chronic hypertension. J Matern Fetal Neonatal Med 2011;24:907–11
  • van Eerd EA, Roex AJ, Nikpoor P, Dekker GA. Adverse perinatal outcome and maternal risk factors in population versus customized defined SGA babies. J Matern Fetal Neonatal Med 2012;25:369–73
  • Robertson WB, Brosens I, Dixon G. Maternal uterine vascular lesions in the hypertensive complications of pregnancy. Perspectives in nephrology and hypertension 1976;5:115–27
  • Brosens IA. Morphological changes in the utero-placental bed in pregnancy hypertension. Clin Obstet Gynaecol 1977;4:573–93
  • Gerretsen G, Huisjes HJ, Elema JD. Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation. Br J Obstet Gynaecol 1981;88:876–81
  • Khong TY, De Wolf F, Robertson WB, Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 1986;93:1049–59
  • Pijnenborg R, Anthony J, Davey DA, et al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 1991;98:648–55
  • Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 2002;187:1416–23
  • Madazli R, Benian A, Ilvan S, Calay Z. Placental apoptosis and adhesion molecules expression in the placenta and the maternal placental bed of pregnancies complicated by fetal growth restriction with and without pre-eclampsia. J Obstet Gynaecol 2006;26:5–10
  • Gilbert JS, Ryan MJ, LaMarca BB, et al. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol 2008;294:H541–50
  • Ogge G, Chaiworapongsa T, Romero R, et al. Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia. J Perinat Med 2011;39:641–52
  • George EM, Granger JP. Linking placental ischemia and hypertension in preeclampsia: role of endothelin 1. Hypertension 2012;60:507–11
  • Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med 1999;222:222–35
  • Myatt L, Kossenjans W, Sahay R, et al. Oxidative stress causes vascular dysfunction in the placenta. J Matern-Fetal Med 2000;9:79–82
  • Potdar N, Singh R, Mistry V, et al. First-trimester increase in oxidative stress and risk of small-for-gestational-age fetus. Bjog 2009;116:637–42
  • Madazli R, Benian A, Aydin S, et al. The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia. J Obstet Gynaecol 2002;22:477–80
  • Cindrova-Davies T. Gabor Than Award Lecture 2008: pre-eclampsia - from placental oxidative stress to maternal endothelial dysfunction. Placenta 2009;30:S55–65
  • Vaughan JE, Walsh SW. Oxidative stress reproduces placental abnormalities of preeclampsia. Hypertension in pregnancy: official journal of the International Society for the Study of Hypertension in Pregnancy 2002;21:205–23
  • Burton GJ, Yung HW, Cindrova-Davies T, Charnock-Jones DS. Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta 2009;30:S43–8
  • Zhou X, Zhang GY, Wang J, et al. A novel bridge between oxidative stress and immunity: the interaction between hydrogen peroxide and human leukocyte antigen G in placental trophoblasts during preeclampsia. Am J Obstet Gynecol 2012;206:447 e447–16
  • Roberts JM, Taylor RN, Musci TJ, et al. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 1989;161:1200–4
  • Chaiworapongsa T, Kim JC, Kim YM, et al. Preeclampsia is characterized by a soluble selectin profile consistent with leukocyte and endothelial cell activation. Am J Obstet Gynecol 2001;185:S74
  • Friedman SA, Schiff E, Emeis JJ, et al. Biochemical corroboration of endothelial involvement in severe preeclampsia. Am J Obstet Gynecol 1995;172:202–3
  • Chaiworapongsa T, Romero R, Yoshimatsu J, et al. Soluble adhesion molecule profile in normal pregnancy and pre-eclampsia. J Matern Fetal Neonatal Med 2002;12:19–27
  • Chaiworapongsa T, Romero R, Gotsch F, et al. Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age. The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 2008;21:41–52
  • Dekker GA, van Geijn HP. Endothelial dysfunction in preeclampsia. Part I: Primary prevention. Therapeutic perspectives. J Perinat Med 1996;24:99–117
  • Roberts JM, Taylor RN, Goldfien A. Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. Am J Hypertens 1991;4:700–8
  • Dekker GA, van Geijn HP. Endothelial dysfunction in preeclampsia. Part II: Reducing the adverse consequences of endothelial cell dysfunction in preeclampsia; therapeutic perspectives. J Perinat Med 1996;24:119–39
  • Roberts JM, Hubel CA. The two stage model of preeclampsia: variations on the theme. Placenta 2009;30:S32–7
  • Taylor RN, de Groot CJ, Cho YK, Lim KH. Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:17–31
  • Bretelle F, Sabatier F, Blann A, et al. Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: comparison with pre-eclampsia. Bjog 2001;108:1277–82
  • Chaiworapongsa T, Espinoza J, Gotsch F, et al. The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation. J Matern Fetal Neona 2008;21:25–40
  • Soto E, Romero R, Richani K, et al. Preeclampsia and pregnancies with small-for-gestational age neonates have different profiles of complement split products. J Matern Fetal Neona 2010;23:646–57
  • Vasey PA, McMahon L, Paul J, et al. A phase II trial of capecitabine (Xeloda) in recurrent ovarian cancer. Br J Cancer 2003;89:1843–8
  • Petrozella L, Mahendroo M, Timmons B, et al. Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period. Am J Obstet Gynecol 2012;207:140 e120–46
  • Siahanidou T, Garatzioti M, Lazaropoulou C, et al. Plasma soluble alpha-klotho protein levels in premature and term neonates: correlations with growth and metabolic parameters. Eur J Endocrinol 2012;167:433–40
  • ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002;77:67–75
  • von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregn 2003;22:143–8
  • Sibai BM, Ewell M, Levine RJ, et al. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol 1997;177:1003–10
  • Alexander GR, Himes JH, Kaufman RB, et al. A United States national reference for fetal growth. Obstet Gynecol 1996;87:163–8
  • Seeds JW. Impaired fetal growth: definition and clinical diagnosis. Obstet Gynecol 1984;64:303–10
  • Chaiworapongsa T, Romero R, Kusanovic JP, et al. Plasma soluble endoglin concentration in pre-eclampsia is associated with an increased impedance to flow in the maternal and fetal circulations. Ultrasound Obstet Gynecol 2010;35:155–62
  • Kurmanavicius J, Florio I, Wisser J, et al. Reference resistance indices of the umbilical, fetal middle cerebral and uterine arteries at 24-42 weeks of gestation. Ultrasound Obstet Gynecol 1997;10:112–20
  • Arduini D, Rizzo G. Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 1990;18:165–72
  • Trudinger BJ, Cook CM, Giles WB, et al. Fetal umbilical artery velocity waveforms and subsequent neonatal outcome. Br J Obstet Gynaecol 1991;98:378–84
  • Semba RD, Cappola AR, Sun K, et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci 2011;66:794–800
  • Yamazaki Y, Imura A, Urakawa I, et al. Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects. Biochem Biophys Res Commun 2010;398:513–18
  • Bloch L, Sineshchekova O, Reichenbach D, et al. Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett 2009;583:3221–4
  • Chen CD, Podvin S, Gillespie E, et al. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A 2007;104:19796–801
  • Akimoto T, Yoshizawa H, Watanabe Y, et al. Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease. BMC Nephrol 2012;13:155
  • Yoon HE, Ghee JY, Piao S, et al. Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy. Nephrol Dial Transplant 2011;26:800–13
  • Wan M, Smith C, Shah V, et al. Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease. Nephrol Dial Transplant 2013;28:153--61
  • Devaraj S, Syed B, Chien A, Jialal I. Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease. Am J Clin Pathol 2012;137:479–85
  • Nagai R, Saito Y, Ohyama Y, et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci 2000;57:738–46
  • Lee J, Jeong DJ, Kim J, et al. The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma. Mol Cancer 2010;9:109
  • Arking DE, Becker DM, Yanek LR, et al. KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet 2003;72:1154–61
  • Kim Y, Kim JH, Nam YJ, et al. Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females. Neurosci Lett 2006;407:189–94
  • Moe SM. Klotho: a master regulator of cardiovascular disease? Circulation 2012;125:2181–3
  • Ohyama Y, Kurabayashi M, Masuda H, et al. Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress. Biochem Biophys Res Commun 1998;251:920–5
  • Ohata Y, Arahori H, Namba N, et al. Circulating levels of soluble alpha-Klotho are markedly elevated in human umbilical cord blood. J Clin Endocrinol Metab 2011;96:E943–7
  • Godang K, Froeslie KF, Henriksen T, et al. Umbilical cord levels of sclerostin, placental weight and birth weight are predictors of total Bone Mineral Content in neonates. Eur J Endocrinol 2013;168:371–8
  • Kaufmann P, Mayhew TM, Charnock-Jones DS. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta 2004;25:114–26
  • Ma R, Gu Y, Groome LJ, Wang Y. ADAM17 regulates TNFalpha production by placental trophoblasts. Placenta 2011;32:975–80
  • Chihara Y, Rakugi H, Ishikawa K, et al. Klotho protein promotes adipocyte differentiation. Endocrinology 2006;147:3835–42
  • Woudenberg-Vrenken TE, van der Eerden BC, van der Kemp AW, et al. Characterization of vitamin D-deficient klotho-/- mice: do increased levels of serum 1,25(OH)2D3 cause disturbed calcium and phosphate homeostasis in klotho-/- mice? Nephrol Dial Transplant 2012;27:4061–8
  • Lu P, Boros S, Chang Q, et al. The beta-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6. Nephrol Dial Transplant 2008;23:3397–402
  • Nakatani T, Sarraj B, Ohnishi M, et al. In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis. Faseb J 2009;23:433–41
  • Sheppard BL, Bonnar J. An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br J Obstet Gynaecol 1981;88:695–705
  • Koukoura O, Sifakis S, Spandidos DA. DNA methylation in the human placenta and fetal growth (review). Mol Med Report 2012;5:883–9
  • Myatt L. Placental adaptive responses and fetal programming. J Physiol 2006;572:25–30
  • Yung HW, Calabrese S, Hynx D, et al. Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction. Am J Pathol 2008;173:451–62
  • Lian IA, Loset M, Mundal SB, et al. Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia. Placenta 2011;32:823–9
  • Benton SJ, Hu Y, Xie F, et al. Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction? Am J Obstet Gynecol 2012;206:163 e161–7
  • Canete P, Monllor A, Pineda A, et al. Levels of heat shock protein 27 in placentae from small for gestational age newborns. Gynecol Obstet Invest 2012;73:248–51
  • Mannik J, Vaas P, Rull K, et al. Differential expression profile of growth hormone/chorionic somatomammotropin genes in placenta of small- and large-for-gestational-age newborns. J Clin Endocrinol Metab 2010;95:2433–42
  • Giannubilo SR, Cecati M, Saccucci F, et al. PP035. Placental klotho protein in preeclampsia: A possible link to long term outcomes. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health 2012;2:260–1
  • Yang Y, Wang Y, Zeng X, et al. Self-control of HGF regulation on human trophoblast cell invasion via enhancing c-Met receptor shedding by ADAM10 and ADAM17. J Clin Endocrinol Metab 2012;97:E1390–401
  • Smith RC, O'Bryan LM, Farrow EG, et al. Circulating alphaKlotho influences phosphate handling by controlling FGF23 production. J Clin Invest 2012;122:4710–15
  • Forster RE, Jurutka PW, Hsieh JC, et al. Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochem Biophys Res Commun 2011;414:557–62
  • Mitchell DM, Juppner H. Regulation of calcium homeostasis and bone metabolism in the fetus and neonate. Curr Opin Endocrinol Diabetes Obes 2010;17:25–30

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