Plasma endothelin levels in preeclampsia: Elevation and correlation with uric acid levels and renal impairment

Clark, Barbara A.; Halvorson, Lisa M.; Sachs, Benjamin P.; Epstein, Franklin H.

doi:10.1016/0002-9378(92)91372-h

Cited by 145 publications

(32 citation statements)

References 20 publications

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“…The ratio of TxA2/PGI2 is elevated after 16 weeks in pre-eclamptic women [15], which may be a marker of the vasoconstrictor versus vasodilator balance. Other alterations are seen in endothelin levels [16], a vasoconstrictor, and nitric oxide [17], a vasodilator.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

Baumwell¹,

Karumanchi²

2007

Nephron Clin Pract

180

111

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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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Section: Clinical Manifestationsmentioning

confidence: 99%

Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

Baumwell¹,

Karumanchi²

2007

Nephron Clin Pract

180

111

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“…ET-1 levels reach 2- to 3-fold higher in the plasma [143], 4- to 8-fold higher in umbilical cord cells [144] and increase in renal tissues during later stages of PE, and return to normal levels within 48 hrs of delivery [145]. ET-1 may be involved in the progression rather than the initiation of PE [146]. Preproendothelin levels show 45% increase in renal cortex and 22% increase in the medulla of RUPP rats [147].…”

Section: Introductionmentioning

confidence: 99%

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Shah

Khalil

2015

Biochemical Pharmacology

151

124

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Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca2+, protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

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“…Preeclampsia has been associated with several mechanisms of disease including defective spiral artery remodeling [15, 39, 55], endothelial cell dysfunction [13, 23, 51, 58, 84, 90, 95, 98, 112, 125], an anti-angiogenic state [4, 17, 19–21, 26, 37, 38, 40, 47, 57, 59–61, 64–68, 70, 73, 75, 78, 91, 99, 105, 115, 121, 122, 127, 130–133, 135, 146], an exaggerated intravascular inflammatory response [7, 18, 22, 45, 48, 71, 72, 76, 77, 93, 94, 97, 109, 119, 120, 128, 129, 134, 142], oxidative stress [28, 52, 82, 83, 138] and a predominantly T helper (Th1)-biased immune response [6, 10, 25, 27, 35, 62, 79, 110, 123, 126, 137, 139]. …”

Section: Introductionmentioning

confidence: 99%

Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods

DiGiulio¹,

Gervasi

Romero³

et al. 2010

Journal of Perinatal Medicine

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Objective Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined. The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia. Method of study Amniotic fluid (AF) from 62 subjects with preeclampsia, not in labor, was analyzed with both cultivation and molecular methods. Broad-range and group-specific PCR assays targeting small subunit ribosomal DNA, or other gene sequences, from bacteria, fungi and archaea were used. Results were correlated with measurements of host inflammatory response, including AF white blood cell count and AF concentrations of glucose, interleukin-6 (IL-6) and MMP-8. Results 1) The rate of MIAC in preeclampsia was 1.6% (1/62) based on cultivation techniques, 8% (5/62) based on PCR, and 9.6% (6/62) based on the combined results of both methods; 2) among the six patients diagnosed with MIAC, three had a positive PCR for Sneathia/Leptotrichia spp.; and 3) patients with MIAC were more likely to have evidence of an inflammatory response in the amniotic cavity than those without MIAC, as determined by a higher median AF IL-6 [1.65 ng/mL interquartile range (IQR): 0.35–4.62 vs. 0.22 ng/mL IQR: 0.12–0.51; P=0.002). Conclusion The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeclampsia. However, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation.

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Plasma endothelin levels in preeclampsia: Elevation and correlation with uric acid levels and renal impairment

Cited by 145 publications

References 20 publications

Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods

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