Article

Pre-eclampsia: Clinical manifestations and molecular mechanisms

Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Nephron Clinical Practice (Impact Factor: 1.65). 02/2007; 106(2):c72-81. DOI: 10.1159/000101801
Source: PubMed

ABSTRACT Preeclampsia affects 3-5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and may reflect different mechanisms of disease. Renal dysfunction and proteinuria correspond to the pathologic finding of glomerular endotheliosis, and generally resolve after cure of preeclampsia through fetal and placenta delivery. The molecular mechanisms behind this disease are being discovered and refined. The initial etiologic agents are currently unknown. Pathologic studies show abnormal development of an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the fetoplacental unit. Endothelial dysfunction plays a central role in the pathogenesis of the maternal syndrome. Dysfunctional endothelial cells produce altered quantities of vasoactive mediators, which lead to a tip in the balance towards vasoconstriction. An imbalance in circulating angiogenic factors is emerging as a prominent mechanism that mediates the endothelial dysfunction and the clinical signs and symptoms of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic factor that is a potent vascular endothelial growth factor (VEGF) antagonist, is highly elevated in preeclampsia. VEGF is not only important in angiogenesis, but also in maintaining endothelial health including the formation of endothelial fenestrae (a hallmark of the glomerular vascular endothelium). sFlt1 overexpression in animals induces glomerular endotheliosis with the loss of endothelial fenestrae that resembles the renal histological lesions of preeclampsia. More severe forms of preeclampsia, including the HELLP syndrome, may be explained by a concomitant elevation in both sFlt1 and soluble endoglin, another anti-angiogenic factor. Unraveling of the molecular mechanisms behind preeclampsia may help to expand our armamentarium to treat patients in a more directed fashion, as current management consists of supportive care and expedited delivery. Finally, long-term outcomes of women with preeclampsia include a significantly increased risk for hypertension and cardiovascular disease, including mortality, which may warrant more aggressive screening and treatment in this population.

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    • "The clinical manifestation varies since PE is associated with several risk factors (obesity, molar pregnancy, hypercoagulation, formation of clots, diabetes mellitus). The prevalence of PE increases up to 66% if there is already an existing chronic kidney disease (Baumwell and Karumanchi 2007). "
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    ABSTRACT: Pre-eclampsia is a serious pathological state affecting 5-10% of pregnant women. Currently, it is diagnosed in the second half of pregnancy, particularly after the 20th week. Symptoms mostly correspond to the changes of blood vessels and kidneys. The severity of pre-eclampsia is proportional to symptomatic manifestations, thus the more symptoms present, the higher is of pre-eclampsia development. Although there are several studies dealing with pre-eclampsia pathology, the complete etiology is still unknown. In this review paper, several theories are presented and discussed.
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    • "Regarding the age and parity, based on world literature, PE is more often developed at young primiparas and older multiparas; actually it has a bimodal probability [9] [10]. Our study, which includes 300 normotensive and 100 pregnancies with developed PE during the pregnancy, conculded that PE is most commonly developed in primiparas. "
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    ABSTRACT: We studied 300 normotensive and 100 PE pregnancies divided into two subgroups: mild (n = 67) and severe (n = 33) PE. This research has included only single pregnancies and the following parameters: maternal age, parity, previous pregnancy history and interval between pregnancies. The study is based on 400 pregnancies with a mean age of 27.65±5.04 years. The significant difference in the frequency of categories and age groups was tested with a method of multivariate analysis for proportion. The difference was not statistically significant P>0.05, which clearly shows that the groups are a priori similar and comparable. Our study shows that PE is most commonly developed in primiparas (P<0.05). The difference was at the level P<0.001. Among women with no history of PE, the median interbirth interval was 4.24 years between the previous and actual pregnancy. Among women with mild PE the median interbirth interval was 5.96 and in group with severe PE was 8.08 years. Multiparous women who are pregnant 5, especially 10 years or more after their previous pregnancy are as likely to have preeclampsia as nulliparous women.
    05/2014; 2:1-6. DOI:10.11131/2014/101065
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    • "Extensive evidence indicates that the placenta of women destined to develop PE releases into the maternal circulation factors that target endothelial cells to cause hypertension and the other clinical manifestations. Many markers of endothelial function are altered, including fibronectin, soluble tissue factor, platelet-derived growth factor, soluble E-selectin, and endothelin (Baumwell and Karumanchi, 2007). There is no question that the features of the disease that are clinically most prominent derive from dysfunctional endothelium. "
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    ABSTRACT: Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, which resolves on placental delivery. It is thought to be the consequence of impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries. In PE the maternal plasma concentration of free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) is decreased whereas the concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and of soluble endoglin (sEng) is increased. These soluble receptors may bind VEGF, PLGF and TGFbeta1 and TGFbeta3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Hence there is a view that the pathogenesis is more or less clarified. According to the vascular theory, poor placentation leads to poor uteroplacental perfusion and hypoxia, which stimulates sFlt-1 and sEng production causing the maternal syndrome. This assumption has been recently challenged. The role of hypoxia as the main stimulus for release of sFlt-1 has been questioned and the role of inflammatory mechanisms has been emphasized. According to this inflammatory theory, poor placentation may predispose more to placental oxidative stress than hypoxia and endothelial dysfunction may be part of a broader disorder of systemic inflammation. Finally, the recent demonstration of activating auto-antibodies to the angiotensin 1 receptor that experimentally play a major pathogenic role in PE further suggests a pleiotropism of aetiologies for this condition. The purpose of this review is to critically evaluate the recent hypotheses and their possible insights on early diagnosis, prevention and treatment.
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