The pathophysiology of preeclampsia in view of the two-stage model

Abstract

A praeeclampsia gyakori és súlyos terhességi kórkép, az anyai és magzati morbiditás és mortalitás egyik vezető oka. A betegség jellemzői a 20. gesztációs hét után kialakult hypertonia és proteinuria, gyakran oedema és több más szubjektív tünet kísérheti. A betegség kiváltó oka a placentában keresendő, a betegség következményei viszont több szervrendszert érintenek. A kétlépcsős modell szerint a placenta kritikus elváltozásai -az abnormális implantá-ció, csökkent lepényi perfúzió -következtében (első lépcső) a keringésbe olyan faktorok kerülnek, amelyek az anyai tünetek megjelenéséért (második lépcső) felelősek. A placenta kórélettanában jelentős szerepet játszik az oxidatív stressz, a nitrogén-monoxid-szintáz enzim csökkent működése, valamint számos sejtes és humorális immunológiai tényező. A manifeszt betegség tüneteinek közös nevezője az endotheldiszfunkció. Az elmélet a hypertonia, proteinuria és oedema triászát és egyéb tünetek eredetét is képes magyarázni. Orv. Hetil., 2012Hetil., , 153, 1167Hetil., -1176 Kulcsszavak: praeeclampsia, nitrogén-monoxid-szintáz, oxidatív stressz, endotheldiszfunkció The pathophysiology of preeclampsia in view of the two-stage modelPreeclampsia is a common and severe disease in pregnancy, a major cause of maternal and fetal morbidity and mortality. The main features of the disease are de novo hypertension after the 20th gestational week and proteinuria, and it is frequently accompanied by edema and other subjective symptoms. The origin of the disease is the placenta, but its sequelae affect multiple organ systems. According to the two-stage model of preeclampsia, the abnormal and hypoperfused placenta (stage 1) releases factors to the bloodstream, which are responsible for the maternal symptoms (stage 2). Oxidative stress, impaired function of nitric-oxide synthase, cellular and humoral immunological factors play an important role in the pathophysiology of the placenta. Endothelial dysfunction is the common denominator of the clinical symptoms. The theory explains the origins of hypertension, proteinuria, edema and other symptoms as well. Orv. Hetil., 2012, 153, 1167-1176 Keywords: preeclampsia, nitric-oxide synthase, oxidative stress, endothelic dysfunction (Beérkezett: 2012. május 16.; elfogadva: 2012. június 7.) Rövidítések ADMA = aszimmetrikus dimetil-arginin; Akt = Akt-kináz, más néven: proteinkináz B (PKB); ASK1 = apoptosis-regulating signal kinase 1; AT1-AA = angiotenzin II 1-es típusú receptorához kötődő agonista hatású antitestek; BH4 = tetrahidrobiopterin; COX = ciklooxigenáz; dNK = decidualis NK-sejt; eNOS = endothelialis nitrogén-monoxid-szintáz; FFA = (free fatty acid) szabad zsírsav; GOT = glutamát/oxálacetát transzamináz; GPT = glutamát/piruvát transzamináz; GTPCH = guanozin-trifoszfát ciklohidroláz; HELLP = haemolyticus anaemia, emelkedett májenzimek, thrombocytopenia; HLA = humán leukocyta-antigén; Hsp90 = hősokkprotein 90; IUGR = intrauterine growth restriction; MAHA = microangiopathiás haemolyticus anaemia; NF-κB = nukleáris faktor kappa-B; PAI = plazminogén...

Preeclampsia: Pathophysiology and the Maternal-Fetal Risk

“…Maternal systemic endothelial cell dysfunction manifests in signs and symptoms that are reflective of maternal vasoconstriction and multi-organ damage outlined in Table 1. Placental hypo perfusion is both a cause and effect of abnormal Placentation [9,10] that becomes more pronounced with growing needs of the feto-placental unit as pregnancy progresses. Late pathologic changes that are seen in the placental tissue correlate with ischemia including atherosis, fibrinoid necrosis, thrombosis, sclerosis of the arterioles, and infarction [11].…”

Role of lncRNA BCYRN1 in trophoblast cell physiology and pathogenesis of preeclampsia

“…The migration, invasion and tube-forming abilities of trophoblast cells are crucial to the establishment of maternal-fetal circulation ( 29 ). Reduced invasive ability of trophoblast cells and subsequent abnormal remodeling of the spiral artery are important features of PE ( 30 ). The number of migratory HTR-8/SVneo cells in the si-BCYRN1 group was significantly decreased compared with that in the si-NC group, whilst the number of migratory cells in the pcDNA3.1-BCYRN1 group was significantly increased compared with the pcDNA3.1 group (all P<0.05; Fig.…”

“…The present study revealed that the apoptosis rate in the si-BCYRN1 group was higher, whilst that in the pcDNA3.1-BCYRN1 group was decreased. Decreased trophoblast proliferation and invasion, and increased apoptosis constitute the main underlying causes of PE ( 30 , 36 ). These previous findings supported the data from the present study that BCYRN1 overexpression increased trophoblast cell proliferation, migration, invasion and tube-forming abilities whilst blocking apoptosis to alleviate PE progression.…”

A Study of HELLP Syndrome among Cases of Pre-Eclampsia and Eclampsia: Incidence and Correlation of Laboratory Parameters

“…The resultant inflammatory response leads to a generalized endothelial dysfunction with activation of complement. The dysfunctional endothelium leads to adherence of platelets and hemolysis leading to ischemic injury to the involved organs, especially liver and results in preeclampsia and HELLP syndrome [4] [14]. The fetus expresses antigens of paternal origin which are foreign to the mother's immune system.…”