پره‌اکلامپسی از دیدگاه سلولی و ملکولی

نوع مقاله : مقاله مروری

نویسندگان

1 دانشجوی کارشناسی ارشد، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه اصفهان، اصفهان، ایران

2 استادیار، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه اصفهان، اصفهان، ایران

3 دانشیار، گروه زنان و زایمان، دانشکده‌ی پزشکی،دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

مقدمه: پره‌اکلامپسی یک اختلال سیستمیک مختص به دوران بارداری است که در 3-5 درصد از بارداری‌ها رخ می‌دهد و عامل اصلی مرگ و میر مادر و نوزاد در سطح جهان، به شمار می‌رود. با وجود دهه‌ها تحقیق و پژوهش، علت این بیماری ناشناخته باقی مانده است و تشخیص آن، قبل از بروز علایم، امکان‌پذیر نمی‌باشد.این مقاله‌ی مروری جنبه‌های مختلف پره‌اکلامپسی را به منظور تشریح پاتوفیزیولوژی آن، بررسی کرد.روش‌ها: مطالعه‌ی کنونی با استفاده از پایگاه‌های اطلاعاتی Ebsco، OVID، Pubmed،  Elsevierو NCBI، به بررسی 96 مقاله منتشرشده پرداخت تا جنبه‌های مختلف پره‌اکلامپسی را شامل سبب‌شناسی، ژنتیک، پروتئومیکس و متابولومیکس تشریح کند.یافته‌ها: بر اساس مطالعات منتشرشده، نقص عملکرد اندوتلیالی و استرس اکسیداتیو، مشکلات اصلی در پره‌اکلامپسی هستند. تاکنون ژن‌های مرتبط و بیومارکرهای مختلفی، گزارش شده‌اند که امید می‌رود بتوانند تشخیص پره‌اکلامپسی را بهبود بخشند. علاوه بر این، پروتئومیکس و متابولومیکس، بینش‌های جدیدی را در رابطه با فهم عوامل ایجادکننده‌ی بیماری و همچنین درمان آن فراهم آورده‌اند.نتیجه‌گیری: پره‌اکلامپسی یک بیماری پیچیده و چند عاملی است که باید از جهات گوناگون مورد ارزیابی قرار گیرد. این مقاله مروری روش‌های جدید برای تشخیص و درمان این اختلال را معرفی می‌نماید.

کلیدواژه‌ها

عنوان مقاله [English]

Preeclampsia in a Cellular and Molecular View

نویسندگان [English]

  • Tayebeh Amirian 1
  • Soheila Rahgozar 2
  • Zahra Shahshahan 3
1 MSc Student, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran
2 Assistant Professor, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran
3 Associate Professor, Department of Obstetrics and Gynecology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Preeclampsia is a multisystem disorder of pregnancy, which complicates 3-5% of pregnancies. It is a major cause of maternal and neonatal mortality worldwide. Despite decades of research, the etiology of preeclampsia has remained unknown and undetectable prior to the onset of symptoms. The current review article discusses different aspects of preeclampsia in order to delineate the pathophysiology of the disease.Methods: This study has reviewed 96 publications explaining the various characteristics of preeclampsia including etiology, genetics, proteomics and metabolomics, using EBSCO, OVID, PubMed, Elsevier and NCBI databases.Findings: Based on the published studies, endothelial dysfunction and oxidative stress are the major problems in preeclampsia. Related genes and biomarkers are reported which may improve the diagnosis of preeclampsia. Proteomics and metabolomics have provided new insights into better understanding of the etiology and management of the disease.Conclusion: Preeclampsia is a complicated and multifactorial disease which needs to be evaluated in different aspects. This review article introduces novel approaches to the diagnosis and treatment of this disorder.

کلیدواژه‌ها [English]

  • Preeclampsia
  • Diagnosis
  • Treatment

مراجع

  1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365(9461): 785-99.
  2. Tranquilli AL, Landi B, Giannubilo SR, Sibai BM. Preeclampsia: no longer solely a pregnancy disease. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health 2012; 2(4): 350-7.
  3. Pettit F, Brown MA. The management of pre-eclampsia: what we think we know. Eur J Obstet Gynecol Reprod Biol 2012; 160(1): 6-12.
  4. Xia Y, Kellems RE. Is preeclampsia an autoimmune disease? Clin Immunol 2009; 133(1): 1-12.
  5. Mohaupt M. Molecular aspects of preeclampsia. Mol Aspects Med 2007; 28(2): 169-91.
  6. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 2011; 25(4): 391-403.
  7. Shahshahan Z, Hashemi M. Crown-rump length discordance in twins in the first trimester and its correlation with perinatal complications. J Res Med Sci 2011; 16(9): 1224-7.
  8. Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol 2009; 200(5): 481-7.
  9. Vigil-De GP. Maternal deaths due to eclampsia and HELLP syndrome. Int J Gynaecol Obstet 2009; 104(2): 90-4.
  10. Curiel-Balsera E, Prieto-Palomino MA, Munoz-Bono J, Ruiz de Elvira MJ, Galeas JL, Quesada GG. Analysis of maternal morbidity and mortality among patients admitted to Obstetric Intensive Care with severe preeclampsia, eclampsia or HELLP syndrome. Med Intensiva 2011; 35(8): 478-83. [In Spanish].
  11. Chadha G, Sood D. Hellp Syndrome-Revisited. Apollo Medicine 2009; 6(3): 242-6.
  12. Jabel Ameli M, Shahshahan Z, Azizian AR. Evaluating the correlation of systemic inflammatory response syndrome with mortality and morbidity in critically Ill obstetric patients in ICU. Qom Univ Med Sci J 2010; 4(1): 37-41.
  13. Bahadoran P, Falahati J, Shahshahan Z, Kianpour M. The comparative examination of the effect of two oxytocin administration methods of labor induction on labor duration stages. Iran J Nurs Midwifery Res 2011; 16(1): 100-5.
  14. Hermes W, van Kesteren F, De Groot CJ. Preeclampsia and cardiovascular risk. Minerva Ginecol 2012; 64(4): 281-92.
  15. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007; 335(7627): 974.
  16. Ferreira I, Peeters LL, Stehouwer CD. Preeclampsia and increased blood pressure in the offspring: meta-analysis and critical review of the evidence. J Hypertens 2009; 27(10): 1955-9.
  17. Wu CS, Nohr EA, Bech BH, Vestergaard M, Catov JM, Olsen J. Health of children born to mothers who had preeclampsia: a population-based cohort study. Am J Obstet Gynecol 2009; 201(3): 269.
  18. Broughton PF, Rubin PC. Pre-eclampsia--the 'disease of theories'. Br Med Bull 1994; 50(2): 381-96.
  19. Newman V, Fullerton JT. Role of nutrition in the prevention of preeclampsia. Review of the literature. J Nurse Midwifery 1990; 35(5): 282-91.
  20. Savelieva GM, Efimov VS, Grishin VL, Shalina RI, Kashezheva AZ. Blood coagulation changes in pregnant women at risk of developing preeclampsia. Int J Gynaecol Obstet 1995; 48(1): 3-8.
  21. Chaouat G, Ledee-bataille N, Zourbas S, Dubanchet S, Sandra O, Martal J, et al. Implantation: can immunological parameters of implantation failure be of interest for pre-eclampsia? J Reprod Immunol 2003; 59(2): 205-17.
  22. Hung TH, Burton GJ. Hypoxia and reoxygenation: a possible mechanism for placental oxidative stress in preeclampsia. Taiwan J Obstet Gynecol 2006; 45(3): 189-200.
  23. Kay H, Nelson M, Wang Y. The placenta: from development to disease. London, UK: Wiley-Blackwell; 2011. p. 246-52.
  24. Redman CW, Sargent IL. Placental stress and pre-eclampsia: a revised view. Placenta 2009; 30(Suppl A): S38-S42.
  25. Meekins JW, Pijnenborg R, Hanssens M, McFadyen IR, van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994; 101(8): 669-74.
  26. Mutze S, Rudnik-Schoneborn S, Zerres K, Rath W. Genes and the preeclampsia syndrome. J Perinat Med 2008; 36(1): 38-58.
  27. Chien PF, Arnott N, Gordon A, Owen P, Khan KS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG 2000; 107(2): 196-208.
  28. Khalil RA, Granger JP. Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models. Am J Physiol Regul Integr Comp Physiol 2002; 283(1): R29-R45.
  29. Bloxam DL, Bullen BE, Walters BN, Lao TT. Placental glycolysis and energy metabolism in preeclampsia. Am J Obstet Gynecol 1987; 157(1): 97-101.
  30. Kim YM, Chaiworapongsa T, Gomez R, Bujold E, Yoon BH, Rotmensch S, et al. Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes. Am J Obstet Gynecol 2002; 187(5): 1137-42.
  31. Myatt L, Cui X. Oxidative stress in the placenta. Histochem Cell Biol 2004; 122(4): 369-82.
  32. 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(Suppl A): S43-S48.
  33. Lian IA, Loset M, Mundal SB, Fenstad MH, Johnson MP, Eide IP, et al. Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia. Placenta 2011; 32(11): 823-9.
  34. Hung TH, Skepper JN, Burton GJ. In vitro ischemia-reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. Am J Pathol 2001; 159(3): 1031-43.
  35. Passam FH, Rahgozar S, Qi M, Raftery MJ, Wong JW, Tanaka K, et al. Beta 2 glycoprotein I is a substrate of thiol oxidoreductases. Blood 2010; 116(11): 1995-7.
  36. Albertin W, Marullo P, Bely M, Aigle M, Bourgais A, Langella O, et al. Linking post-translational modifications and variation of phenotypic traits. Mol Cell Proteomics 2013; 12(3): 720-35.
  37. Passam FH, Rahgozar S, Qi M, Raftery MJ, Wong JW, Tanaka K, et al. Redox control of beta2-glycoprotein I-von Willebrand factor interaction by thioredoxin-1. J Thromb Haemost 2010; 8(8): 1754-62.
  38. Ioannou Y, Zhang JY, Passam FH, Rahgozar S, Qi JC, Giannakopoulos B, et al. Naturally occurring free thiols within beta 2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress-induced cell injury. Blood 2010; 116(11): 1961-70.
  39. Appella E, Anderson CW. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 2001; 268(10): 2764-72.
  40. Seo J, Lee KJ. Post-translational modifications and their biological functions: proteomic analysis and systematic approaches. J Biochem Mol Biol 2004; 37(1): 35-44.
  41. Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med 2008; 264(3): 224-36.
  42. Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, et al. A redox switch in angiotensinogen modulates angiotensin release. Nature 2010; 468(7320): 108-11.
  43. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation 2012; 126(6): 753-67.
  44. Kestlerova A, Feyereisl J, Frisova V, Mechurova A, Sula K, Zima T, et al. Immunological and biochemical markers in preeclampsia. J Reprod Immunol 2012; 96(1-2): 90-4.
  45. Bayram M, Bostanci MS, Celtemen MB, Bagrlaclk EU, Yaman M, Civil F. Maternal inflammatory response in severe preeclamptic and preeclamptic pregnancies. J Clin Gynecol Obstet 2012; 1(2-3): 40-5.
  46. Redman CW, Sargent IL. Preeclampsia and the systemic inflammatory response. Semin Nephrol 2004; 24(6): 565-70.
  47. Burton GJ, Yung HW. Endoplasmic reticulum stress in the pathogenesis of early-onset pre-eclampsia. Pregnancy Hypertens 2011; 1(1-2): 72-8.
  48. Bdolah Y, Karumanchi SA, Sachs BP. Recent advances in understanding of preeclampsia. Croat Med J 2005; 46(5): 728-36.
  49. Salonen RH, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet 2000; 91(4): 256-60.
  50. O'shaughnessy KM, Ferraro F, Fu B, Downing S, Morris NH. Identification of monozygotic twins that are concordant for preeclampsia. Am J Obstet Gynecol 2000; 182(5): 1156-7.
  51. Bernard N, Giguere Y. Genetics of preeclampsia: what are the challenges? J Obstet Gynaecol Can 2003; 25(7): 578-85.
  52. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005; 308(5728): 1592-4.
  53. Mitchell R, Kumar V, Fausto N, Abbas AK, Aster J. Pathologic basis of disease. 8th ed. Philadelphia, PA: Saunders Elsevier; 2011. p.1057–8.
  54. Skjaerven R, Vatten LJ, Wilcox AJ, Ronning T, Irgens LM, Lie RT. Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort. BMJ 2005; 331(7521): 877.
  55. Haig D. Genetic conflicts in human pregnancy. Q Rev Biol 1993; 68(4): 495-532.
  56. Colhoun HM, McKeigue PM, Davey SG. Problems of reporting genetic associations with complex outcomes. Lancet 2003; 361(9360): 865-72.
  57. Wang JX, Knottnerus AM, Schuit G, Norman RJ, Chan A, Dekker GA. Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet 2002; 359(9307): 673-4.
  58. Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 2002; 20: 217-51.
  59. Hiby SE, Walker JJ, O'shaughnessy KM, Redman CW, Carrington M, Trowsdale J, et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 2004; 200(8): 957-65.
  60. Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 2005; 5(3): 201-14.
  61. LaMarca BD, Ryan MJ, Gilbert JS, Murphy SR, Granger JP. Inflammatory cytokines in the pathophysiology of hypertension during preeclampsia. Curr Hypertens Rep 2007; 9(6): 480-5.
  62. Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 2000; 157(6): 2111-22.
  63. Perkins AV. Endogenous anti-oxidants in pregnancy and preeclampsia. Aust N Z J Obstet Gynaecol 2006; 46(2): 77-83.
  64. Kim YJ, Williamson RA, Chen K, Smith JL, Murray JC, Merrill DC. Lipoprotein lipase gene mutations and the genetic susceptibility of preeclampsia. Hypertension 2001; 38(5): 992-6.
  65. Zusterzeel PL, Peters WH, Burton GJ, Visser W, Roelofs HM, Steegers EA. Susceptibility to pre-eclampsia is associated with multiple genetic polymorphisms in maternal biotransformation enzymes. Gynecol Obstet Invest 2007; 63(4): 209-13.
  66. Akolekar R, Etchegaray A, Zhou Y, Maiz N, Nicolaides KH. Maternal serum activin a at 11-13 weeks of gestation in hypertensive disorders of pregnancy. Fetal Diagn Ther 2009; 25(3): 320-7.
  67. Atkinson KR, Blumenstein M, Black MA, Wu SH, Kasabov N, Taylor RS, et al. An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia. J Lipid Res 2009; 50(1): 71-80.
  68. Laivuori H, Lahermo P, Ollikainen V, Widen E, Haiva-Mallinen L, Sundstrom H, et al. Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families. Am J Hum Genet 2003; 72(1): 168-77.
  69. Lachmeijer AM, Arngrimsson R, Bastiaans EJ, Frigge ML, Pals G, Sigurdardottir S, et al. A genome-wide scan for preeclampsia in the Netherlands. Eur J Hum Genet 2001; 9(10): 758-64.
  70. Zintzaras E, Kitsios G, Harrison GA, Laivuori H, Kivinen K, Kere J, et al. Heterogeneity-based genome search meta-analysis for preeclampsia. Hum Genet 2006; 120(3): 360-70.
  71. Roten LT, Johnson MP, Forsmo S, Fitzpatrick E, Dyer TD, Brennecke SP, et al. Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study). Eur J Hum Genet 2009; 17(2): 250-7.
  72. Ark M, Yilmaz N, Yazici G, Kubat H, Aktas S. Rho-associated protein kinase II (rock II) expression in normal and preeclamptic human placentas. Placenta 2005; 26(1): 81-4.
  73. Johnson MP, Roten LT, Dyer TD, East CE, Forsmo S, Blangero J, et al. The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Hum Genet 2009; 126(5): 655-66.
  74. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet 2008; 40(3): 340-5.
  75. Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409(6822): 928-33.
  76. Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 1993; 4(1): 59-61.
  77. Caulfield M, Lavender P, Newell-Price J, Kamdar S, Farrall M, Clark AJ. Angiotensinogen in human essential hypertension. Hypertension 1996; 28(6): 1123-5.
  78. GOPEC Consortium. Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study. Am J Hum Genet 2005; 77(1): 127-31.
  79. Tuteja G, Cheng E, Papadakis H, Bejerano G. PESNPdb: a comprehensive database of SNPs studied in association with pre-eclampsia. Placenta 2012; 33(12): 1055-7.
  80. Webster RP, Myatt L. Elucidation of the molecular mechanisms of preeclampsia using proteomic technologies. Proteomics Clin Appl 2007; 1(9): 1147-55.
  81. Moxon JV, Padula MP, Herbert BR, Golledge J. Challenges, current status and future perspectives of proteomics in improving understanding, diagnosis and treatment of vascular disease. Eur J Vasc Endovasc Surg 2009; 38(3): 346-55.
  82. Carty DM, Delles C, Dominiczak AF. Novel biomarkers for predicting preeclampsia. Trends Cardiovasc Med 2008; 18(5): 186-94.
  83. Kalkunte S, Lai Z, Norris WE, Pietras LA, Tewari N, Boij R, et al. Novel approaches for mechanistic understanding and predicting preeclampsia. J Reprod Immunol 2009; 83(1-2): 134-8.
  84. Mary S, Patil GV, Kulkarni AV, Kulkarni MJ, Joshi SR, Mehendale SS, et al. Dynamic proteome in enigmatic preeclampsia: an account of molecular mechanisms and biomarker discovery. Proteomics Clin Appl 2012; 6(1-2): 79-90.
  85. Gharesi-Fard B, Zolghadri J, Kamali-Sarvestani E. Proteome differences of placenta between pre-eclampsia and normal pregnancy. Placenta 2010; 31(2): 121-5.
  86. Kim YN, Kim HK, Warda M, Kim N, Park WS, Prince AB, et al. Toward a better understanding of preeclampsia: Comparative proteomic analysis of preeclamptic placentas. Proteomics Clin Appl 2007; 1(12): 1625-36.
  87. Buhimschi IA, Zhao G, Funai EF, Harris N, Sasson IE, Bernstein IM, et al. Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia. Am J Obstet Gynecol 2008; 199(5): 551-16.
  88. Carty DM, Siwy J, Brennand JE, Zurbig P, Mullen W, Franke J, et al. Urinary proteomics for prediction of preeclampsia. Hypertension 2011; 57(3): 561-9.
  89. Watanabe H, Hamada H, Yamada N, Sohda S, Yamakawa-Kobayashi K, Yoshikawa H, et al. Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia. Proteomics 2004; 4(2): 537-43.
  90. Heitner JC, Koy C, Kreutzer M, Gerber B, Reimer T, Glocker MO. Differentiation of HELLP patients from healthy pregnant women by proteome analysis--on the way towards a clinical marker set. J Chromatogr B Analyt Technol Biomed Life Sci 2006; 840(1): 10-9.
  91. Kenny LC, Dunn WB, Ellis DI, Myers J, Baker PH, Kell DB, et al. Novel biomarkers for pre-eclampsia detected using metabolomics and machine learning. Metabolomics 2005; 1(3): 227-34.
  92. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, et al. Metabolomics and first-trimester prediction of early-onset preeclampsia. J Matern Fetal Neonatal Med 2012; 25(10): 1840-7.
  93. Odibo AO, Goetzinger KR, Odibo L, Cahill AG, Macones GA, Nelson DM, et al. First-trimester prediction of preeclampsia using metabolomic biomarkers: a discovery phase study. Prenat Diagn 2011; 31(10): 990-4.
مجله دانشکده پزشکی اصفهان
دوره 31، شماره 234 - شماره پیاپی 234
خرداد و تیر 1392
صفحه 568-580

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  • تاریخ دریافت: 27 دی 1391
  • تاریخ بازنگری: 12 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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