Maternal endothelial function and serum concentrations of placental growth factor and soluble endoglin in women with abnormal placentation

Savvidou, Makrina D.; Noori, Muna; Anderson, James M.; Hingorani, Aroon D.; Nicolaides, Kypros H.

doi:10.1002/uog.6126

Cited by 51 publications

(42 citation statements)

References 53 publications

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“…Thus, there is similarity between the observations made with flow cytometry in these "Great Obstetrical Syndromes", and those that we report by examining the concentrations of angiogenic and anti-angiogenic factors (e.g. preeclampsia [38][39][40][41][42][43][44][45][47][48][49][50][51][52][53][54][55][56], pregnancies with SGA fetuses and abnormal Doppler velocimetry [57][58][59], "mirror syndrome" [61], TTTS [62] and unexplained fetal death [63].…”

Section: Clinical Implicationsupporting

confidence: 76%

“…Elevated plasma sEng concentrations have been reported in obstetrical conditions with perturbation of blood supply to the uterus such as preeclampsia [38][39][40][41][42][43][44][45]48,49,51,52,56], and pregnancies with fetal growth restriction [57][58][59]. Evidence suggests that over-expression of Eng on trophoblasts could inhibit trophoblast differentiation and invasion during placentation [85,86].…”

Section: Plasma Concentrations Of Pro-angiogenic and Anti-angiogenic mentioning

confidence: 99%

“…However, the precise mechanisms responsible for the onset of preterm parturition in cases of ischemia have not been determined. Recently, an imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes with perturbation in utero-placental blood supply including preeclampsia [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56], fetal growth restriction [57][58][59], placental abruption [60], "mirror syndrome" [61], twin-to-twin transfusion syndrome(TTTS) [62] and unexplained fetal death [63]. Angiogenesis, a process by which new vessels are formed from pre-existing vasculature, is regulated by several growth factors, cytokines and their receptors, including fibroblast growth factors, transforming growth factors, hepatocyte growth factors, angiogenins, angiopoietins, ephrins, and vascular endothelial growth factors (VEGF) [64,65].…”

Section: Introductionmentioning

confidence: 99%

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A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

Chaiworapongsa¹,

Romero²,

Tarca³

et al. 2009

DJMF

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OBJECTIVE-An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction, and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and antiangiogenic factors different from normal pregnant women.STUDY DESIGN-This longitudinal nested case-control study included normal pregnant women (n=208) and patients with PTL leading to preterm delivery (n=52). Maternal blood samples were collected at 6 gestational age intervals from 6-36.9 weeks of gestation. The end point (time of diagnosis) of the study, "True PTL", was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. RESULTS-1)Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of "true NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript PTL". 2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of "true PTL"; and 3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patents diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. CONCLUSION-The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition.

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Section: Clinical Implicationsupporting

confidence: 76%

Section: Plasma Concentrations Of Pro-angiogenic and Anti-angiogenic mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

Chaiworapongsa¹,

Romero²,

Tarca³

et al. 2009

DJMF

View full text Add to dashboard Cite

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“…[19][20][21][22][23][24][25] Together with endothelial dysfunction, these have become the biochemical hallmarks of severe preeclampsia. Few studies have investigated the functions of CSE/H 2 S in pregnancy.…”

mentioning

confidence: 99%

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

et al. 2013

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H ydrogen sulfide (H 2 S), a gaseous signaling molecule, promotes vasodilatation 1 and stimulates angiogenesis in the vasculature.2 H 2 S has anti-inflammatory properties 3 and is also cytoprotective against cellular damage induced by lethal hypoxia or reperfusion injury. 4,5 Cystathionine γ-lyase (CSE) is the principal enzyme responsible for the endogenous production of H 2 S.6 Chronic administration of the CSE inhibitor DL-propargylglycine (PAG) leads to elevated blood pressure and vascular remodeling in the rat, 7 and both CSE and H 2 S levels are reduced in pulmonary hypertensive rats. 8Mice genetically deficient in CSE develop age-dependent hypertension, severe hyperhomocysteinemia, and endothelial dysfunction. 9 Clearly, H 2 S has multiple roles in health and disease, 10,11 but its role in pregnancy-induced hypertension is unknown. Editorial see p 2472 Clinical Perspective on p 2522Preeclampsia is a hypertensive syndrome that affects 4% to 7% of all pregnancies and is a major contributor to maternal and fetal morbidity and mortality worldwide. 12 The exact etiology of preeclampsia is unknown; abnormal placentation 13,14 and imbalance in angiogenic factors 15,16 have been implicated in preeclampsia pathogenesis. Importantly, circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), the endogenous inhibitor of vascular endothelial growth factor and placental Background-The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H 2 S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Methods and Results-Plasma levels of H 2 S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8-12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H 2 S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect ...

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“…47,48 In line with these observations, numerous studies have concluded that women who subsequently develop PE demonstrate impaired endothelium-dependent vasodilation early in pregnancy. 8,49,50 Abnormal vascular function has been shown to persist postpartum after PE, and it may provide an explanation for the significant risk of cardiovascular disease later in life. 8,10,12 Indeed, an important outstanding question is whether abnormal endothelial biology is a cause or a consequence of PE disorders.…”

Section: Vascular Dysfunction In Pementioning

confidence: 99%

Current Theories on the Prevention of Severe Preeclampsia With Low-Molecular Weight Heparin

et al. 2015

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Maternal endothelial function and serum concentrations of placental growth factor and soluble endoglin in women with abnormal placentation

Abstract: Objectives To determine whether maternal serum concentrations of placental growth factor (PlGF) PlGF (154.8 ± 150.8 vs. 423.3 ± 230.5 pg/mL; P < 0.001) (data given as mean ± SD) and higher levels of sEng (8.1 (7.0-14.1) vs. 6.5 (4.9-7.9)

Cited by 51 publications

References 53 publications

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

Current Theories on the Prevention of Severe Preeclampsia With Low-Molecular Weight Heparin

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