Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes

Wijk, Marja J. van; Boer, Kees; Nisell, Henry; Smárason, Alexander K.; VanBavel, Ed; Kublickiene, Karolina

doi:10.1016/s0306-5456(01)00221-2

Cited by 14 publications

(13 citation statements)

References 20 publications

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“…Also, studies on human umbilical vein ECs co-cultured with STBM cells isolated from normal and PE placentas have suggested that endothelial cell-to-cell junctions are sensitive targets for STBM-derived factors, leading to increased EC permeability [60]. Other studies do not support the STBM deportation theory and have shown that intraluminal perfusion of isolated myometrial arteries of Norm-Preg women with STBM concentrations up to 100 times those reported in PE does not affect bradykinin-induced dilation or cause significant damage to the endothelium [61]. …”

Section: Introductionmentioning

confidence: 99%

Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy

Sheppard¹,

Khalil²

2010

CHDDT

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Normal pregnancy is associated with significant hemodynamic changes and vasodilation in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. Hypertension in pregnancy (HTN-Preg) and preeclampsia (PE) are major complications and life-threatening conditions to both the mother and fetus. PE is precipitated by various genetic, dietary and environmental factors. Although the initiating events of PE are unclear, inadequate invasion of cytotrophoblasts into the uterine artery is thought to reduce uteroplacental perfusion pressure and lead to placental ischemia/hypoxia. Placental hypoxia induces the release of biologically active factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and antibodies to vascular angiotensin II receptor. These bioactive factors affect the production/activity of various vascular mediators in the endothelium, smooth muscle and extracellular matrix, leading to severe vasoconstriction and HTN. As an endothelial cell disorder, PE is associated with decreased vasodilator mediators such as nitric oxide, prostacyclin and hyperpolarizing factor and increased vasoconstrictor mediators such as endothelin, angiotensin II and thromboxane A2. PE also involves enhanced mechanisms of vascular smooth muscle contraction including intracellular free Ca2+ concentration ([Ca2+]i), and [Ca2+]i sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Changes in extracellular matrix composition and matrix metalloproteases activity also promote vascular remodeling and further vasoconstriction in the uterine and systemic circulation. Characterization of the predisposing risk factors, the biologically active factors, and the vascular mediators associated with PE holds the promise for early detection, and should help design specific genetic and pharmacological tools for the management of the vascular dysfunction associated with HTN-Preg.

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Section: Introductionmentioning

confidence: 99%

Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy

Sheppard¹,

Khalil²

2010

CHDDT

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“…Peripheral vein plasmas from pregnant women suffering from pre‐eclampsia had a significantly greater effect than plasmas from normal, matched controls, 7 consistent with the fact that more of the particles are shed in pre‐eclampsia 3 . In vitro , STBM have been shown to cause a loss of endothelium‐dependent relaxation in perfused small subcutaneous human arteries, 8 although not all authors agree 9 . Apart from interacting directly with the endothelial cells, STBM may be capable of binding to and activating circulating monocytes, thereby stimulating the release of proinflammatory cytokines (G. P. Sacks, D.Phil thesis, University of Oxford; unpubl.…”

Section: Introductionmentioning

confidence: 86%

“…3 In vitro, STBM have been shown to cause a loss of endothelium-dependent relaxation in perfused small subcutaneous human arteries, 8 although not all authors agree. 9 Apart from interacting directly with the endothelial cells, STBM may be capable of binding to and activating circulating monocytes, thereby stimulating the release of proinflammatory cytokines (G. P. Sacks, D.Phil thesis, University of Oxford; unpubl. obs., 1998).…”

Section: Introductionmentioning

confidence: 99%

Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells

Hoegh

Tannetta

Sargent

et al. 2006

BJOG

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Objective Syncytiotrophoblast membrane fragments (STBM) exist in the peripheral circulation in pregnant women and it has been shown that the level of circulating STBM is significantly increased with pre-eclampsia compared with uncomplicated pregnancies. STBM could be one of the factors which directly causes the endothelial cell dysfunction of pre-eclampsia. This study investigates the effect of STBM on endothelial cell gene expression.Design Human umbilical vein endothelial cells were cultured in the presence and absence of STBM. At specified time points, total RNA was purified from the cultures and analysed on microarrays.Setting A laboratory investigation using placentas obtained from a hospital delivery ward.Sample Placentas from nine healthy women were obtained. STBM vesicles were isolated from the placentas and umbilical vein endothelial cell cultures were established from the umbilical cords.Methods Gene expression was screened by Affymetrix GeneChips and confirmed with real-time polymerase chain reaction or enzyme-linked immunosorbent assay.Main outcome measures Fold changes in gene expression levels between treated and control cultures were calculated from the microarray results.Results Overall, the results do not show any great changes in gene expression in endothelial cells after STBM treatment (28 genes changed two-fold or more out of approximately 10 000 genes examined by microarray). In general, the changes observed are consistent with inhibition of proliferation of endothelial cells by exposure to STBM. The unfolded protein response in particular may be involved.Conclusions STBM may influence endothelial cell function during pregnancy but STBM alone cannot account for the entire range of endothelial dysfunctions observed in pre-eclampsia.

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“…The disturbance in endothelial cell-to-cell junctions was associated with a significant increase in endothelial cell permeability, which may translate into increased vascular permeability in vivo [21]. However, other studies do not support the trophoblast deportation theory as a cause of vascular dysfunction in PE and have shown that intraluminal perfusion of isolated myometrial arteries of healthy pregnant women with syncytiotrophoblast microvillous membranes at concentrations up to 100 times those reported in PE do not affect bradykinin-induced dilation or cause significant damage to the endothelium [22]. The preliminary characterization of the putative biologically active factor(s) in PE plasma suggested a high-molecular-weight protein/glycoprotein, with possible contributions from a hydrophobic, lipophilic factor [23].…”

Section: Biologically Active Factors Involved In Hypertension In Pregmentioning

confidence: 95%

Interactions of Biologically Active Factors and Vascular Mediators During Hypertension in Pregnancy

Stennett¹,

Khalil²

2007

CHYR

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Normal pregnancy is associated with changes in the cardiovascular system, including vascular remodeling of the uterine and systemic circulation in order to meet the metabolic demands of the developing fetus. These cardiovascular changes are due to alterations in the amount/activity of vascular mediators such as nitric oxide, prostacyclin and endothelin in the endothelium; calcium and protein kinase C in the smooth muscle; and metalloproteases in the extracellular matrix. Hypertension in pregnancy is a major complication, and can lead to life threatening neurovascular disorders. It has been suggested that hypertension in pregnancy may develop from an inadequate invasion of cytotrophoblasts into the uterine artery, causing reduction in the uteroplacental perfusion pressure, and resulting in placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of various biologically active factors such as cytokines, reactive oxygen species, and hypoxia-inducible factors. Elevated plasma/tissue levels of these factors during pregnancy could cause vascular dysfunction, vasoconstriction and hypertension. The purpose of this review is to discuss the interactions between biologically active circulating factors and vascular mediators, released during preeclampsia as compared to those released in other conditions characterized by hypoxia, in order to provide insight into the sequence of events that leads to the development of hypertension in pregnancy.

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Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes

Cited by 14 publications

References 20 publications

Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy

Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy

Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells

Interactions of Biologically Active Factors and Vascular Mediators During Hypertension in Pregnancy

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