Vasoactivity to and Endogenous Release of Vascular Endothelial Growth Factor in the in vitro Perfused Human Placental Lobule from Pregnancies Complicated by Preeclampsia

Brownbill, Paul; Mills, Thomas M.; Soydemir, Didem; Sibley, Colin P.

doi:10.1016/j.placenta.2008.08.020

Cited by 28 publications

(21 citation statements)

References 37 publications

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“…50 In this study, cord plasma PlGF levels were below the detection limit in both groups, and similar findings were previously reported. 51,15 In our study, sFlt-1 levels in cord plasma were increased, although they were not significant in preeclampsia, consistent with earlier reports. 51 Some studies have also shown that infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF levels.…”

Section: Discussionsupporting

confidence: 92%

“…51,15 In our study, sFlt-1 levels in cord plasma were increased, although they were not significant in preeclampsia, consistent with earlier reports. 51 Some studies have also shown that infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF levels. 9,45,46 Levels of angiogenic factors may be regulated differently in the maternal and cord plasma of preeclamptic women.…”

Section: Discussionsupporting

confidence: 92%

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Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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This study was designed to test the hypothesis that altered angiogenic factors together with increased oxidative stress and reduced docosahexaenoic acid (DHA) levels may be associated with altered birth outcome parameters. To test this hypothesis, levels of plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), the oxidative stress marker malondialdehyde (MDA) and fatty acids were estimated in women with preeclampsia and their cord samples and compared with those in normotensive women. The association of these parameters with birth outcome was also examined. Our results show that in preeclamptic women, maternal plasma VEGF and PlGF levels were lower, whereas sFlt-1 levels were higher (Po0.05 for all) than in normotensive women. In contrast, cord plasma VEGF levels were higher (Po0.05) in preeclamptic women, whereas there was no difference in sFlt-1 levels. Plasma DHA levels in both the mother and cord were lower (Po0.05) in the preeclamptic group compared with normotensive women. Maternal plasma sFlt-1 levels were positively (n¼23, r¼0.415, P¼0.039) associated with MDA concentrations in preeclamptic women. Maternal plasma sFlt-1 levels showed a strong negative association with baby weight (n¼37, r¼À0.547, P¼0.001), head circumference (n¼37, r¼À0.472, P¼0.005) and baby chest circumference (n¼37, r¼À0.375, P¼0.032) in the preeclamptic group. Cord plasma sFlt-1 concentrations were negatively associated with cord plasma DHA concentrations (n¼28, r¼À0.552, P¼0.004). This study suggests that dysregulation of angiogenic factors may be associated with maternal oxidative stress. Increased oxidative stress may reduce cord DHA levels and increase sFlt-1 levels, leading to poor birth outcomes in preeclampsia.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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“…In experiments using in vitro isolated perfused lobules of the human placenta from normal pregnancies and those affected by PET, Brownbill et al 36 observed that VEGF-165 applied to the fetal-side circulation was a potent vasodilator of the fetoplacental vasculature. However, we did not observe any difference in umbilical artery Doppler parameters in these longterm or in previous short-term experiments (4 --7 days post vector injection).…”

Section: Discussionmentioning

confidence: 99%

Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A165 in the uterine arteries of pregnant sheep

et al. 2011

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“…[16][17][18] Although little is known about the placental release of these factors into the fetoplacental circulation under conditions of reduced oxygen tension, it has been recently demonstrated that there is reduction in VEGF and an increased in vitro placental release of the soluble VEGF receptor (sVEGFR-1), and PlGF into the fetal side in PE placental tissue compared with the tissue from normal pregnancy. 19 The overall aim of this project was to enable perfusion of the placental cotyledon at soluble oxygen levels appropriate to normoxic normal physiology and hypoxic pathophysiology and investigate placental VEGF endocrinology under different oxygen tensions. We hypothesized that hypoxic perfusion would reduce free VEGF levels as a secondary consequence of sVEGFR-1 upregulation.…”

mentioning

confidence: 99%

“…20 PlGF levels were hypothesized to be elevated during hypoxic perfusion, in keeping with observations of higher levels in fetal cord serum of pre-eclamptic pregnancy, compared with normal pregnancy. 19 Our first objective was to modify the in vitro dually perfused placental cotyledon system so that perfusion took place under conditions relevant to normoxia found in health and hypoxia anticipated to occur in PE. In the normoxic and hypoxic adaptations, we aimed for an average initial physiological oxygen tension of around 5-7% and o3% within the IVS, respectively, which might be different over a sustained period of time.…”

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confidence: 99%

Adapting in vitro dual perfusion of the human placenta to soluble oxygen tensions associated with normal and pre-eclamptic pregnancy

Soydemir

Kuruvilla

Brown³

et al. 2011

Laboratory Investigation

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For decades, superoxic ex vivo dual perfusion of the human placental lobule has been used as a model to study the physiology and metabolism of the placenta. The aim of this study was to further develop the technique to enable perfusion at soluble oxygen concentrations similar to those in normal pregnancy (normoxia) and in pre-eclampsia (PE; hypoxia). Our design involved reducing the mean soluble oxygen tension in the maternal-side intervillous space (IVS) perfusate to 5-7% and o3% for normoxia and hypoxia, respectively, while providing a more ubiquitous delivery of perfusate into the IVS, using 22 maternal-side cannulae. We achieved quasi-steady states in [O 2 ] fetal venous (soluble) , which were statistically different between the two adaptations at t ¼ 150 to t ¼ 240 min of dual perfusion (2.1, 1.2, 2.8 and 0.4, 0.0, 1.5%; median, 25th, 75th percentiles, n ¼ 20 and 24 readings in n ¼ 5 and n ¼ 6 lobules, normoxic and hypoxic perfusion, respectively; Po0.001, Mann-Whitney U-test). Lactate dehydrogenase (LDH) levels in fetal and maternal venous outflow perfusates were unaffected by the adaptations. There was also no difference in tissue lactate release between the two adaptations. Glucose consumption from the fetal circulation and maternal-side 'venous' pyruvate release were higher under normoxic conditions, indicative of a greater metabolic flux through glycolysis. Furthermore, there was greater release of the hypoxic-sensitive marker, macrophage inflammatory protein-1a, into the maternal venous perfusate in the hypoxic model. Also, during hypoxic perfusion, we found that fetal-side venous placental growth factor (PlGF) levels were higher compared with normoxic perfusion. We conclude that these ex vivo adapted methods of placental perfusion provide a means of studying aspects of placental metabolism in relation to normal oxygenation and hypoxia-associated pregnancy disease.

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Vasoactivity to and Endogenous Release of Vascular Endothelial Growth Factor in the in vitro Perfused Human Placental Lobule from Pregnancies Complicated by Preeclampsia

Cited by 28 publications

References 37 publications

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A165 in the uterine arteries of pregnant sheep

Adapting in vitro dual perfusion of the human placenta to soluble oxygen tensions associated with normal and pre-eclamptic pregnancy

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