scholarly journals 15-Lipoxygenase-1 Prevents Vascular Endothelial Growth Factor A– and Placental Growth Factor–Induced Angiogenic Effects in Rabbit Skeletal Muscles via Reduction in Growth Factor mRNA Levels, NO Bioactivity, and Downregulation of VEGF Receptor 2 Expression

2008 ◽  
Vol 102 (2) ◽  
pp. 177-184 ◽  
Author(s):  
Helena Viita ◽  
Johanna Markkanen ◽  
Emmi Eriksson ◽  
Markku Nurminen ◽  
Kati Kinnunen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Skeletal Muscles ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Rabbit Skeletal Muscles

scholarly journals Vascular Pool of Releasable Soluble VEGF Receptor-1 (sFLT1) in Women With Previous Preeclampsia and Uncomplicated Pregnancy

2014 ◽  
Vol 99 (3) ◽  
pp. 978-987 ◽  
Author(s):  
Tracey L. Weissgerber ◽  
Augustine Rajakumar ◽  
Ashley C. Myerski ◽  
Lia R. Edmunds ◽  
Robert W. Powers ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Whole Blood ◽  
Placental Growth Factor ◽  
Potential Contribution ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Uncomplicated Pregnancy ◽  
Heparin Plasma ◽  
Endothelial Growth Factor

Context: Research examining the source of excess soluble fms-like tyrosine kinase 1 (sFLT1) in preeclampsia has focused on the placenta. The potential contribution of the releasable store of sFLT1 in the systemic vasculature is unknown. Objective: We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy. Design: We administered heparin to nulligravid women and to women with previous preeclampsia or a previous uncomplicated pregnancy. We compared post-heparin sFLT1 concentrations with those observed in uncomplicated pregnancy and preeclampsia. Setting: The study was performed at Magee-Womens Hospital. Patients: Participants included nulligravidas (n = 8), women 6–24 months postpartum (previous uncomplicated pregnancy, n = 16; previous preeclampsia, n = 15), and pregnant women (uncomplicated pregnancy, n = 30; preeclampsia, n = 25). Intervention: Nonpregnant women received an unfractionated heparin bolus. Main Outcome Measures: Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured. Results: In nonpregnant women, heparin increased plasma sFLT1 by 250-fold (P < .01), increased placental growth factor by 7-fold (P < .01), and decreased free vascular endothelial growth factor (P < .01). These changes did not differ between nulligravidas, women with previous preeclampsia, and women with a previous uncomplicated pregnancy. Post-heparin sFLT1 in nonpregnant women was higher than sFLT1 in uncomplicated pregnancy, but lower than sFLT1 in preeclampsia. Baseline and post-heparin sFLT1 were positively correlated (r2 = 0.19; P < .01). Heparin increased the concentration of the 100-kDa sFLT1 isoform. Adding heparin to whole blood or plasma did not increase sFLT1. Conclusions: Nonpregnant women have a significant vascular store of releasable sFLT1. The size of this store does not differ between women with previous preeclampsia vs women with previous uncomplicated pregnancy.

Model of competitive binding of vascular endothelial growth factor and placental growth factor to VEGF receptors on endothelial cells

2004 ◽  
Vol 286 (1) ◽  
pp. H153-H164 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Synergistic Effects ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Relative Contribution ◽  
Endothelial Growth Factor

Placental growth factor (PlGF) competes with vascular endothelial growth factor (VEGF) for binding to VEGF receptor (VEGFR)-1 but does not bind VEGFR2. Experiments show that PlGF can augment the response to VEGF in pathological angiogenesis and in models of endothelial cell survival, migration, and proliferation. This synergy has been hypothesized to be due to a combination of the following: signaling by PlGF through VEGFR1 and displacement of VEGF from VEGFR1 to VEGFR2 by PlGF, causing increased signaling through VEGFR2. In this study, the relative contribution of PlGF-induced VEGF displacement to the synergy is quantified using a mathematical model of ligand-receptor binding to examine the effect on ligand-receptor complex formation of VEGF and PlGF acting together. Parameters specific to the VEGF-PlGF system are used based on existing data. The model is used to simulate in silico a specific in vitro experiment in which VEGF-PlGF synergy is observed. We show that, whereas a significant change in the formation of endothelial surface growth factor-VEGFR1 complexes is predicted in the presence of PlGF, the increase in the number of VEGFR2-containing signaling complexes is less significant; these results were shown to be robust to significant variation in the kinetic parameters of the model. Synergistic effects observed in that experiment thus appear unlikely to be due to VEGF displacement but to a shift from VEGF-VEGFR1 to PlGF-VEGFR1 complexes and an increase in total VEGFR1 complexes. These results suggest that VEGFR1 signaling can be functional in adult-derived endothelial cells.

scholarly journals Low-Dose Dopamine Agonist Administration Blocks Vascular Endothelial Growth Factor (VEGF)-Mediated Vascular Hyperpermeability without Altering VEGF Receptor 2-Dependent Luteal Angiogenesis in a Rat Ovarian Hyperstimulation Model

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5400-5411 ◽  
Author(s):  
Raul Gomez ◽  
Miguel Gonzalez-Izquierdo ◽  
Ralf C. Zimmermann ◽  
Edurne Novella-Maestre ◽  
Isabel Alonso-Muriel ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Low Dose ◽  
Specific Treatment ◽  
Vegf Receptor ◽  
Ovarian Hyperstimulation ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Serum Progesterone ◽  
Endothelial Growth Factor

No specific treatment is available for ovarian hyperstimulation syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hypersecretion of vascular endothelial growth factor (VEGF)-activating VEGF receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist (SU5416). However, due to its toxicity (thromboembolism) and disruption of VEGFR-2-dependent angiogenic processes critical for pregnancy, this kind of compound cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists, used in the treatment of human hyperprolactinemia including pregnancy, inhibit VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal cancer models. To test whether VEGFR-2-dependent VP and angiogenesis could be segregated in a dose-dependent fashion with the Dp-r2 agonist cabergoline, a well-established OHSS rat model supplemented with prolactin was used. A 100 μg/kg low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2 phosphorylation levels. No luteolytic effects (serum progesterone levels and luteal apoptosis unaffected) were observed. Cabergoline administration also did not affect VEGF/VEGFR-2 ovarian mRNA levels. Results in the animal model and the safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline to oocyte donors at high risk for developing the syndrome. Prophylactic administration of cabergoline (5–10 μg/kg·d) decreased the occurrence of OHSS from 65% (controls) to 25% (treatment). Therefore, a specific, safe treatment for OHSS is now available.

scholarly journals Overexpression of the Soluble Vascular Endothelial Growth Factor Receptor in Preeclamptic Patients: Pathophysiological Consequences

2003 ◽  
Vol 88 (11) ◽  
pp. 5555-5563 ◽  
Author(s):  
Vassilis Tsatsaris ◽  
Frederic Goffin ◽  
Carine Munaut ◽  
Jean-François Brichant ◽  
Marie-Rose Pignon ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Vegf Receptor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Membrane Bound ◽  
Endothelial Growth Factor

Abstract Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.

Early predictors of placental dysfunction

2016 ◽  
pp. 25-28
Author(s):  
J.M. Melnik ◽  
◽  
A.A. Shlyahtina ◽  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Umbilical Artery ◽  
Placental Growth Factor ◽  
Vascular Endothelial ◽  
Endothelin 1 ◽  
Placental Dysfunction ◽  
Early Predictors ◽  
Endothelial Growth Factor

The article presents the predictors of placental dysfunction on the early stage of pregnancy. The objective: the search for prognostic markers and criteria for the occurrence of placental insufficiency in the early stages of the gestational process to optimize the pregnancy and labor with improved perinatal outcomes. Patients and methods. To solve this goal in the period from 2013 to 2015 were conducted a comprehensive survey of 334 pregnant women, which depending on the peculiarities of pregnancy and childbirth were divided into groups. The control group consisted of 236 pregnant women with uncomplicated gestational period, no morphological signs of placental dysfunction. The study group included 98 patients with a complicated pregnancy who had revealed violations of the fetal-placental relations, which was confirmed by morphological examination of the placenta in the postpartum period. Results. It was found that pregnant women with placental insufficiency in the first trimester of pregnancy have higher levels of interleukin-1B (IL-1v) and interleukin-3 (IL-3) in comparison with physiological pregnancy, as well as there is a direct significant correlation between IL-1v and pulsative index (PI) in the spiral (r=0.84) and uterine artery (r=0.77), and the inverse correlation between the level of IL-3 and PI in the terminal branches of the umbilical artery (r=-0.69). Verified an inverse relationship between the concentration of endothelin-1, the level of vascular endothelial growth factor (r=-0.87) and placental growth factor (r=-0.73), and also a direct link between the content of endothelin-1 and PI in spiral arteries (r=0.89), uterine artery (r=0.83) and the terminal branches of the umbilical artery (r=0.79). Conclusion. Thus, it is proven that early predictors of placental dysfunction can be considered the concentration of endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin-1, interleukin-3, and the indices of pulsative index. Key words: placental dysfunction, predictors, endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin, pulsative index.

Sign in / Sign up

Export Citation Format

Share Document