Angiogenic imbalances: the obstetric perspective

Espinoza, Jimmy; Uckele, John E.; Starr, Robert A.; Seubert, David; Espinoza, Andres F.; Berry, Stanley M.

doi:10.1016/j.ajog.2009.10.891

Cited by 43 publications

(76 citation statements)

References 147 publications

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“…In contrast, late-onset preeclampsia is less commonly associated with severe placental disease, and consequently exhibits less dramatic alterations in the circulating levels of placentalderived angiogenic proteins [8,10]. Late-onset preeclampsia may largely be influenced by maternal factors, including features of metabolic syndrome occurring later in gestation [11][12][13]. Women who develop late-onset disease typically exhibit a normal or rather exaggerated haemodynamic response to pregnancy [5].…”

Section: Preeclampsia Preventionmentioning

confidence: 99%

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

McLaughlin

Scholten

Parker

et al. 2018

Brit J Clinical Pharma

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Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization. Preeclampsia preventionPreeclampsia is a hypertensive disorder of pregnancy, clinically diagnosed by new-onset hypertension after 20 weeks' gestation with evidence of organ injury [1]. The potential maternal and perinatal complications of preeclampsia are significant, including maternal seizures, fetal growth restriction (FGR) and stillbirth. Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2]. Early-onset preeclampsia is hypothesized to be a direct consequence of the interactions between a dysfunctional placenta and maternal cardiovascular system, while late-onset preeclampsia is hypothesized to be largely triggered by maternal constitutional factors [3][4][5]. Typically, women with early-onset preeclampsia present with an acute, severe syndrome that threatens the life of both the mother and her fetus. In contrast, late-onset preeclampsia is a less severe illness with a favourable clinical outcome in countries with well-developed maternity systems. However, in countries with limited medical resources, preeclampsia remains among the most frequent causes of maternal death [6].The early-and late-onset subsets of preeclampsia exhibit different types and severity of placental pathologies and express divergent maternal haemodynamics. Early-onset preeclampsia is strongly associated with placental disease characterized by maternal vascular malperfusion, where the abnormal placental villi secrete excessive amounts of antiangiogenic proteins and reduced levels of pro-angiogenic proteins into the maternal circulation [7][8][9]. Women with early-onset disease, typically associated with FGR, develop hypertension earlier in pregnancy that is characterized by increased systemic vascular resistance, reduced cardiac output and stroke volume along with relative bradycardia [5]. In contrast, late-onset preeclampsia is less commonly associated with severe placental disease, and consequently exhibits less British Journal of Clinical Pharmacology Br J Clin Pharmacol (2018) 84 673-678 673

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Section: Preeclampsia Preventionmentioning

confidence: 99%

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

McLaughlin

Scholten

Parker

et al. 2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…It is possible that a combination of some of these mechanisms may be responsible for the manifestations of the clinical spectrum of preeclampsia. For example, the following experimental and clinical evidences suggest that uteroplacental ischemia result in maternal hypertension and increased circulating concentrations of anti-angiogenic factors: (1) reduced uterine perfusion in nonhuman primates 53 and rats 33 is associated with hypertension and increased placental expression of anti-angiogenic factors; (2) cytotrophoblast cultured under hypoxic conditions upregulates the mRNA expression and production of sFlt-1 in the supernatant 54 ; (3) increased expression of sFlt-1 of human placental is mediated by hypoxia inducible factor-1 (HIF-1) 55 ; (4) among patients with preeclampsia, the higher the impedance to blood flow in the uterine arteries (a surrogate maker of chronic uteroplacental ischemia), the higher the maternal plasma concentration of anti-angiogenic factors 56 and (5) histological lesions suggestive of chronic trophoblast ischemia have been associated with hypertension, proteinuria and angiogenic imbalances, including lesions consistent with "maternal underperfussion" in "classic preeclampsia" 57 , severe villous oedema in "Mirror Syndrome" and "avascular" villi in mole and partial mole 58 . Another example of how a combination of the above-mentioned mechanisms of injury may be operative in preeclampsia is the recent report that deported trophoblast, specifically syncytial knot aggregates detached from the placenta, may account for 25% of measurable circulating sFlt-1 in the third trimester in normal pregnant women and in those with preeclampsia 59 .…”

Section: Angiogenic Imbalances In Preeclampsiamentioning

confidence: 99%

“…We proposed that the dose response between the magnitude of uteroplacental ischemia and the timing of the development of preeclampsia suggests that there is an absolute or relative "trophoblast ischemic threshold" beyond which preeclampsia develops 82 . It is possible that the response to this threshold may be modified by gene-environment interaction 64 , the magnitude of angiogenic imbalances 58,133 and fetal signalling in response to absolute or relative uteroplacental ischemia 134,135 .…”

Section: Angiogenic Imbalances In Molar Pregnancies and Partial Molementioning

confidence: 99%

Angiogenic Imbalances in the Pathogenesis of Pregnancy Complications

Espinoza

2014

Fet. Matern. Med. Rev.

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Endothelial cell proliferation and survival require continuous low levels of vascular endothelial growth factor (VEGF). The bioavailability of this angiogenic factor appears to be regulated by anti-angiogenic factors, including the soluble form of VEGF receptor 1 (sFlt-1) in the non-pregnant and pregnant states. During pregnancy a VEGF antagonist (sFlt-1) and other anti-angiogenic factors, including soluble endoglin (s-Eng), are produced by the human placenta and released into the maternal circulation; an excess of these anti-angiogenic factors can lead into angiogenic imbalances and pregnancy complications. This is important because regulation of VEGF action on angiogenic balances appears to be essential for a successful pregnancy.

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“…These pregnancy complications are character- ized by the presence of "avascular placental villi" or placental villi with capillary remnants. 10 Thus, by definition, mole and partial mole may represent an extreme in the spectrum of ischemic disease of the trophoblast. 10 The dose-response between the magnitude of uteroplacental ischemia and the timing of the development of preeclampsia suggests that there is an absolute or relative "trophoblast ischemic threshold" beyond which preeclampsia develops.…”

Section: Uteroplacental Ischemia: Early-onset Preeclampsia and Fetal mentioning

confidence: 99%

“…10 Thus, by definition, mole and partial mole may represent an extreme in the spectrum of ischemic disease of the trophoblast. 10 The dose-response between the magnitude of uteroplacental ischemia and the timing of the development of preeclampsia suggests that there is an absolute or relative "trophoblast ischemic threshold" beyond which preeclampsia develops. This threshold may be modified by a gene-environment interaction, the magnitude of angiogenic imbalances, and fetal signaling in response to absolute or relative uteroplacental ischemia.…”

Section: Uteroplacental Ischemia: Early-onset Preeclampsia and Fetal mentioning

confidence: 99%

Abnormal Fetal–Maternal Interactions

Espinoza

2012

Obstetrics & Gynecology

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There is clinical and ultrasonographic evidence that "abnormal fetal-maternal interactions" or "fetal-maternal conflicts" may be central to the mechanisms of injury in pregnancy complications such as fetal growth restriction, preeclampsia, fetal death, gestational diabetes, and a subset of patients with preterm parturition. This conceptual framework integrates abnormalities in the placental bed, placental vasculature, and other areas of fetal-maternal interactions with pregnancy complications in light of their possible evolutionary value.

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Angiogenic imbalances: the obstetric perspective

Cited by 43 publications

References 147 publications

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

Angiogenic Imbalances in the Pathogenesis of Pregnancy Complications

Abnormal Fetal–Maternal Interactions

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