PREECLAMPSIA: Parte 2°: fisiopatologia e trattamento

Abstract

Preeclampsia

Preeclampsia is a pregnancy-specific disorder usually defined as new-onset hypertension and proteinuria after the 20^th week of gestation. Preeclampsia is a systemic disease with multiorgan involvement, and it is associated with a high risk of maternal and fetal morbidity and mortality. To date its pathogenesis is not completely understood, but placental hypoxia or hypoxia/reoxigenation may be the basic condition leading to systemic inflammation and endothelial dysfunction that induce all the clinical manifestations of the disorder. Delivery is the only curative treatment. Indeed, for the management of preeclampsia one needs to consider both the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery.

Keywords

Preeclampsia Endotheliosis Hypoxia reoxigenation Endothelial dysfunction

Get full access to this article

View all access options for this article.

References

Von Dadelszen

Magee

Roberts

JM.

Subclassification of preeclampsia. Hypertens Pregnancy 2003; 22(2):143–148.

Staff

Jhnsen

Dechend

et al . Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol 2014; 101–102:120–126.

Lim

Zhou

Janatpour

et al . Human cytotrophoblast differeniation/invasioni is abnormal in pre-eclampsia. Am J Pathol 1997; 151:1809–1818.

Alexander

Llinas

Kruckeberg

et al . L-arginine attenuates hpertension in pregnant rats wth reduced uterine perfusion pressure. Hypertension 2004; 43:832–836.

Gomez

Figueras

Martinez

et al . Squentia changes in uterine artery blood flow pattern beween the first and second trimesters of gestation in relation to pregnancy outcome. Ultrasound Obstet Gynecol 2006; 28:802–808.

Roberts

JM.

Preeclampsia: What we know and what we don’t know. Semin Perinatol 2000; 24:24–28.

Jauniaux

Watson

Hempstock

et al . Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pegnancy failure. Am J Pathol 2000; 157;2111–2122.

Hung

Graham

JB.

Hypoxia and reoxigenation: a possible mechanism for placental oxidative stress in preeclampsia. Taiwanese J Obstet Gynecol 2006; 45(3):189–200.

Watson

Skepper

Jauniaux

et al . Susceptibiity of human placental syncytiotrophbastic mitochondria to oxygen-mediated damage in relation to gestational age. J Clin Endocr Metab 1998; 83:1697–1705.

10.

Mouithys-Michalad

Sluse

FE.

Generation of superoxide anion by mitochondria and imparment of their function during anoxia and reoxygenation in vitro. Free Radic Biol Med 1998; 25:1066–1074.

11.

Granger

Korthuis

RJ.

Physiologic mechanisms of postischemic tissue injury. Annu Rev Physiol 1995; 57:311–332.

12.

Wang

Walsh

SW.

Placental mitochondria as a source of oxidative stress in pre-eclampsia. Placenta 1998; 19:581–586.

13.

Rinehart

Terrone

Lagoo-Deenadayalan

et al . Expression of the placental cytokines tumor necrosis factor alpha, interleukin 1 beta, and interleukin 10 is increased in preeclampsia. Am J Obstet Gynecol 1999; 181:915–920.

14.

Wang

Walsh

SW.

TNF alpha concentration and mRNA expression are increased in preeclamptic placentas. J Reprod Immunol 1996; 32:157–169.

15.

Hajjar

Silverstein

et al . Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J Exp Med 1987; 166:235–245.

16.

Marsden

Brenner

BM.

Transcriptional regulation of the endothelin -1 gene by TNF-alpha. Am J Physiol 1992; 262:C854–C861.

17.

van Hisbergh

Kooistra

van der Berg

et al . Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood 1998; 72:1467–1473.

18.

von Dadelszen

Magee

Roberts

et al . Sublassification of preeclampsia. Hypertens Pregnancy 2003; 22(2):143–148.

19.

Sohlberg

Mulic-Lutvica

Lindgren

et al . Placental perfusion in normal pregnancy and early and late preeclampsia: a magnetic resonance imaging study. Placenta 2014; 35(3):202–206.

20.

Mariuzzi

Cavazzini

Patologia della gravidanza. In Lanza G Anatomia patologica sistemica 1978, Ed Piccin.

21.

Lees

Hill

Ochner

III et al . Maternal placental and myometrial blod flow of the Rhesus monkey during uterine contractions. Am J Obstet Gynecol 1971; 110:68–81.

22.

Borell

Fernstrom

Ohlson

et al . An arteriographic study of the blood flow through the uterus and the placenta at midpregnancy. Acta Obstet Gynaecol Scand 1965; 44:22–31.

23.

Meekins

Pijnenborg

Hanssens

et al . A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynecol 1994; 101:669–674.

24.

Doridot

Passet

Mehats

et al . Preeclampsia-like symptoms induced in mice by fetoplacental expression of STOX1 are reversed by aspirin treatment. Hypertension 2013; 61:662–668.

25.

Burton

Jauniaux

Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 2018; 218(2S):S745–S768.

26.

Milosevic-Stevanovic

Krstic

Radovic-Janosevic

et al . Preeclampsia with and without intrauterine growth restriction–Two pathogenetically different entities? Hypertens Pregnancy 2016; 35(4):573–582.

27.

Doridot

Passet

Méhats

et al . Preeclampsia-like symptoms induced in mice by fetoplacental expression of STOX1 are reversed by aspirin treatment. Hypertension 2013; 61:662–668.

28.

Afshar

Jeong

Roqueiro

et al . Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse. FASEB J 2012; 26:282–294.

29.

Cobellis

Mastrogiacomo

Federico

et al . Distribution of Notch protein members in normal and preeclampsia-complicated placentas. Cell Tissue Res 2007; 330:527–534.

30.

White

Brost

Sun

et al . Normal early pregnancy: transient state of epigenetic change favoring hypomethylation. Epigenetics 2012; 7:729–734.

31.

White

Brost

Sun

et al . Genome-wide methylation profiling demonstrates hypermehylation in maternal leukocyte DNA in preeclamptic compared normotensive pregnancies. Hyperten Pregnancy 2013; 32:257–269.

32.

Burma

Cohen

Veraar

et al . Preeclampsia is characterized by placental complement dysregulation. Hyertension 2012; 60:1332–1337.

33.

Wang

Hao

et al . Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010; 84:164–70.

34.

Saito

Sakai

Th1/Th2 balance in preeclampsia. J Reprod Immunol 2003; 59(2):161–173.

35.

Hanna

Goldman-Wohl

Hamani

et al . Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 2006; 12(9):1065–1074.

36.

Zhang

Gong

Jia

et al . Studies on activity of NK cells in preeclampsia patients. J Huazhong Univ Sci Technolog Med Sci 2004; 24(5):473–475.

37.

Verdonk

Visser

Van Den Meiracker

et al . The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad. Clin Sci (Lond) 2014; 126(8):537–544.

38.

Xia

Kellems

RE.

Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond. Circ Res 2013; 113(1):78–87.

39.

Kobayashi

Yamamoto

Chishima

et al . Autoantibodies isolated from patients with preeclampsia induce soluble endoglin production from trophoblast cells via interactions with angiotensin II type 1 receptor. Am J Reprod Immunol 2015; 73:285–291.

40.

Wenzel

Rajakumar

Haase

et al . Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats. Hypertension 2011; 58(1):77–84.

41.

Dragun

Muller

Brasen

et al . Angiotensin ii type 1-receptor activating antibodies in renal-allograft rejection. New Eng J Med 2005; 352:558–569.

42.

Wong

Zhao

Stevenson

DK.

A deficiency in haem oxgenase-1 induces fetal growth restriction by placental vasculature defects. Acta Paediatr 2012; 101:827–834.

43.

McCaig

Lyall

Inhibitors of heme oxyenase reduce invasionof human primary cytotrophoblast cellsin vitro. Placenta 2009; 30:536–538.

44.

Cao

Inoue

et al . Physiologic signficance of heme oxyenase in hypertension. Int J biochem Cell Biol 2009; 41:1025–1033.

45.

Cudmoe

Ahmad

Al-Ani

et al . Negative regulation of soluble Flt-1 and soluble endoglin release by heme oygenae-1. Circulation 2007; 115:1789–1797.

46.

Baum

Schiff

Kreisr

et al . End-tidal carbo monoxide measurements in women ith pregancy-induced hypertension and preclampsia. Am J Obstet Gynecol 2000; 183:900–903.

47.

Wikström

Stephansson

Cnattingius

Tobacco use during pregnancy and preclampsia risk: effects of cigarette smoking and snuff. Hypertension 2010; 55:1254–1259.

48.

Zhai

Guo

Smith

et al . Maternal exposure to moderate ambient carbon monoxide is asociated with decreased risk of preeclampsia. Am J Obstet Gynecol 2012; 207:57. e1-e9.

49.

Govender

Naicker

Moodley

Maternal imbalance between proangiogenic and anti-angiogenic factors in HIV-infected women with pre-eclampsia. Cardiovasc J Afr 2013; 24(5):174–179.

50.

Maynard

Min

Merchan

et al . Excess placental soluble fmslike tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003; 111(5):649–658.

51.

Sibai

Dekker

Kupfeminc

Pre-eclampsia. Lancet

2005; 365:785–799.

52.

Jenkins

Head

Hauth

JC.

Severe preeclampsia at 25 weeks of gestation: maternal and neonatal outcomes. Am J Obstet Gynecol 2002; 186:790–795.

53.

Budden

Wilkinson

Buksh

et al . Pregnancy outcome in women presenting with pre-eclampsia at less than 25 weeks gestation. Aust NZJ Obstet Gynaecol 2006; 46:407–412.

54.

Haddad

Deis

Goffinet

et al . Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation. Am J Obstet Gynecol 2004; 190:1590–1595.

55.

Société française d’anesthésie et de réanimation. Collège national des gynécologues et obstétriciens français. Société française de médecine périnatale. Société française de néonatalogie. Multidisciplinary management of severe pre-eclampsia (PE). Experts’ guidelines 2008. Ann Fr Anesth Reanim 2009; 28:275–281.

56.

Pottecher

Luton

Prise en Charge Multidisciplinaire de la Prééclampsie. Issy Les Moulineaux, France: Elsevier Masson SAS 2009.

57.

Koopmans

Bijlenga

Groen

et al . Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009; 374:979–988.

58.

Haddad

Sibai

BM.

Expectant management in pregnancies with severe preeclampsia. Semin Perinatol 2009; 33:143–151.

59.

Kee-Ha

Preeclampsia, Medscape, 2018 Feb 16. https://emedicine.medscape.com/article/1476919-overview#a2 accessed 20 febbraio 2018

60.

Maronzio

Benedetto

La preeclamsia. Linee Guida AIPE 2013. http://www.sigo.it/wp-content/uploads/2015/10/linee-guida-aipe-20131.pdf accessed 20 febbraio 2018

61.

Thadhani

Kisner

Hagmann

et al . Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia. Circulation 2011; 124:940–950.

62.

Thadhani

Hagmann

Schaarschmidt

et al . Removal of soluble fms-like tyrosine kinase-1 by dextran sulfate apheresis in preeclampsia. JASN 2016; 27:903–913.

63.

Onda

Tong

Beard

et al . Proton pump inhibitors decrease soluble fms-like tyrosine kinase-1 and soluble endoglin secretion, decrease hypertension, and rescue endothelial dysfunction. Hypertension 2017; 69:457–468.

64.

Saleh

Samantar

Garrelds

I M

et al . Low soluble fms-like tyrosine kinase-1, endoglin, and endothelin-1 levels in women with confirmed or suspected preeclampsia using proton pump inhibitors. Hypertension 2017; 70:594–600.

65.

Spradley

Tan

Joo

et al . Placental growth factor administration abolishes placental ischemia-induced hypertension. Hypertension 2016; 67:740–747.

66.

Kumasawa

Ikawa

Kidoya

et al . Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc Natl Acad Sci USA 2011; 108:1451–1455.

67.

Zhang

Ying Ma

et al . Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension 2007; 50;686–692.

68.

Bergmann

Ahmad

Cudmore

et al . Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J Cell Mol Med 2010; 14:1857–1867.

69.

Saleh

Verdonk

Visser

et al . The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis 2016; 10:282–293.

70.

Bakrania

Duncan

Warrington

Granger

JP.

The endothelin type a receptor as a potential therapeutic target in preeclampsia. Int J Mol Sci 2017; 18:E522.