Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells

Zhang, Hong Hai; Chen, Jennifer C.; Sheibani, Lili; Lechuga, Thomas J.; Chen, Dong Bao

doi:10.1210/jc.2017-00437

Cited by 33 publications

(41 citation statements)

References 37 publications

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“…Another important mediator of endothelial dysfunction in pre-eclampsia is the potent vasodilator and antioxidant NO, which has been shown to mediate the effects of PlGF and VEGF in vitro 111,117,118 . Circulating levels of NO are reduced in women with preeclampsia [119][120][121] , whereas restoration of bioavailable NO seems to attenuate the elevation in sFLT1 and hypertension that is seen in pregnant rats with NO synthesis inhibition 122 .…”

Section: Maternal Syndromementioning

confidence: 99%

Pre-eclampsia: pathogenesis, novel diagnostics and therapies

et al. 2019

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Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. The disease presents with new-onset hypertension and often proteinuria in the mother, which can progress to multi-organ dysfunction, including hepatic, renal and cerebral disease, if the fetus and placenta are not delivered. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-eclampsia. Risk factors for the disease include maternal comorbidities, such as chronic kidney disease, hypertension and obesity; a family history of pre-eclampsia, nulliparity or multiple pregnancies; and previous preeclampsia or intrauterine fetal growth restriction. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. In this Review, we discuss the pathogenic role of antiangiogenic proteins released by the placenta in the development of pre-eclampsia and review novel therapeutic strategies directed at restoring the angiogenic imbalance observed during pre-eclampsia. We also highlight other notable advances in the field, including the identification of long-term maternal and fetal risks conferred by pre-eclampsia.

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Section: Maternal Syndromementioning

confidence: 99%

Pre-eclampsia: pathogenesis, novel diagnostics and therapies

et al. 2019

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“…Estrogens also stimulate the production of the potent endogenous vasodilator, hydrogen sulfide (H 2 S), which is higher in EC and SMC of UA from pregnant women and during the estrus stage of the menstrual cycle [111]. In human UAEC, it was shown that VEGF upregulated H 2 S-forming enzymes, probably via the actions of VEGF ( Figure 2) [112].…”

Section: Estrogens As Endogenous Vasodilator Peptidesmentioning

confidence: 99%

Influence of Estrogens on Uterine Vascular Adaptation in Normal and Preeclamptic Pregnancies

Mandalà

2020

IJMS

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During pregnancy, the maternal cardiovascular system undergoes significant changes, including increased heart rate, cardiac output, plasma volume, and uteroplacental blood flow (UPBF) that are required for a successful pregnancy outcome. The increased UPBF is secondary to profound circumferential growth that extends from the downstream small spiral arteries to the upstream conduit main uterine artery. Although some of the mechanisms underlying uterine vascular remodeling are, in part, known, the factors that drive the remodeling are less clear. That higher circulating levels of estrogens are positively correlated with gestational uterine vascular remodeling suggests their involvement in this process. Estrogens binding to the estrogen receptors expressed in cytotrophoblast cells and in the uterine artery wall stimulate an outward hypertrophic remodeling of uterine vasculature. In preeclampsia, generally lower concentrations of estrogens limit the proper uterine remodeling, thereby reducing UPBF increases and restricting the growth of the fetus. This review aims to report estrogenic regulation of the maternal uterine circulatory adaptation in physiological and pathological pregnancy that favors vasodilation, and to consider the underlying molecular mechanisms by which estrogens regulate uteroplacental hemodynamics.

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“…We have developed novel human UAEC and UASMC models from pregnant and nonpregnant women for uterine hemodynamics research. In these cells, we found that pregnancy augments VEGF-stimulated H 2 S production by the selective upregulation of CBS expression, without altering CSE expression in vitro [250]. Primary human UAEC retains the pregnancy-dependent expression of ERα and ERβ in culture.…”

Section: Hydrogen Sulfidementioning

confidence: 78%

Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy

Bai

et al. 2020

IJMS

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Normal pregnancy is associated with dramatic increases in uterine blood flow to facilitate the bidirectional maternal–fetal exchanges of respiratory gases and to provide sole nutrient support for fetal growth and survival. The mechanism(s) underlying pregnancy-associated uterine vasodilation remain incompletely understood, but this is associated with elevated estrogens, which stimulate specific estrogen receptor (ER)-dependent vasodilator production in the uterine artery (UA). The classical ERs (ERα and ERβ) and the plasma-bound G protein-coupled ER (GPR30/GPER) are expressed in UA endothelial cells and smooth muscle cells, mediating the vasodilatory effects of estrogens through genomic and/or nongenomic pathways that are likely epigenetically modified. The activation of these three ERs by estrogens enhances the endothelial production of nitric oxide (NO), which has been shown to play a key role in uterine vasodilation during pregnancy. However, the local blockade of NO biosynthesis only partially attenuates estrogen-induced and pregnancy-associated uterine vasodilation, suggesting that mechanisms other than NO exist to mediate uterine vasodilation. In this review, we summarize the literature on the role of NO in ER-mediated mechanisms controlling estrogen-induced and pregnancy-associated uterine vasodilation and our recent work on a “new” UA vasodilator hydrogen sulfide (H2S) that has dramatically changed our view of how estrogens regulate uterine vasodilation in pregnancy.

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Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells

Abstract: Comparisons between NP- and P-hUAECs reveal that pregnancy augments VEGF-stimulated in vitro angiogenesis and NO/H2S production in hUAECs, showing that the newly established hUAEC model provides a critical in vitro tool for understanding human uterine hemodynamics.

Cited by 33 publications

References 37 publications

Pre-eclampsia: pathogenesis, novel diagnostics and therapies

Pre-eclampsia: pathogenesis, novel diagnostics and therapies

Influence of Estrogens on Uterine Vascular Adaptation in Normal and Preeclamptic Pregnancies

Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy

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