KH902, a Recombinant Human VEGF Receptor Fusion Protein, Reduced the Level of Placental Growth Factor in Alkali Burn Induced-Corneal Neovascularization

2013 ◽  
Vol 50 (3) ◽  
pp. 180-186 ◽  
Author(s):  
Ai-Yi Zhou ◽  
Yu-Jing Bai ◽  
Min Zhao ◽  
Wen-Zhen Yu ◽  
Xiao-Xin Li
Keyword(s):  
Growth Factor ◽  
Fusion Protein ◽  
Corneal Neovascularization ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Alkali Burn

scholarly journals An unexpected tail of VEGF and PlGF in pre-eclampsia

2011 ◽  
Vol 39 (6) ◽  
pp. 1576-1582 ◽  
Author(s):  
David O. Bates
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Activation ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Physiological Changes ◽  
Vegf Family Members ◽  
Endothelial Growth Factor ◽  
Vegf Isoforms

PET (pre-eclamptic toxaemia), characterized by pregnancy-related hypertension and proteinuria, due to widespread endothelial dysfunction, is a primary cause of maternal morbidity. Altered circulating factors, particularly the VEGF (vascular endothelial growth factor) family of proteins and their receptors, are thought to be key contributors to this disease. Plasma from patients with PET induces numerous cellular and physiological changes in endothelial cells, indicating the presence of a circulating imbalance of the normal plasma constituents. These have been narrowed down to macromolecules of the VEGF family of proteins and receptors. It has been shown that responses of endothelial cells in intact vessels to plasma from patients with pre-eclampsia is VEGF-dependent. It has recently been shown that this may be specific to the VEGF165b isoform, and blocked by addition of recombinant human PlGF (placental growth factor). Taken together with results that show that sVEGFR1 (soluble VEGF receptor 1) levels are insufficient to bind VEGF-A in human plasma from patients with pre-eclampsia, and that other circulating macromolecules bind, but do not inactivate, VEGF-A, this suggests that novel hypotheses involving altered bioavailability of VEGF isoforms resulting from reduced or bound PlGF, or increased sVEGFR1 increasing biological activity of circulating plasma, could be tested. This suggests that knowing how to alter the balance of VEGF family members could prevent endothelial activation, and potentially some symptoms, of pre-eclampsia.

Placental Growth Factor (PlGF) Synergizes with Granulocyte Colony-Stimulating Factor (G-CSF) for the Mobilization of Primitive and Committed Peripheral Blood Progenitor Cells (PBPCs) in Nonhuman Primates.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4994-4994
Author(s):  
Carmelo Carlo-Stella ◽  
Massimo Di Nicola ◽  
Paolo Longoni ◽  
Raffaella Milani ◽  
Marco Milanesi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Nonhuman Primates ◽  
Fold Increase ◽  
Placental Growth Factor ◽  
Proliferative Potential ◽  
Vegf Receptor ◽  
Primate Model ◽  
Cell Counts ◽  
Baseline Values ◽  
The Absolute

Abstract Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family which signals through VEGF receptor-1. In mice, administration of an adenoviral vector expressing human PlGF accelerates bone marrow recovery following myelosuppression and mobilizes PBPCs. By injecting either murine or human PlGF alone, we failed to detect any PBPC mobilization in mice, whereas the combined injection of PlGF plus G-CSF resulted in a 2- to 4-fold increase of PBPCs. Due to the relevant clinical impact of any procedure capable of improving PBPC mobilization, we tested the mobilizing activity of PlGF (Geymonat S.p.A., Anagni, Italy) as an adjunct to G-CSF in a nonhuman primate model. A cohort of Rhesus Monkeys (n = 4) was initially mobilized with G-CSF alone (100 μg/kg/day, SC, for 5 days) (cycle 1), and after a 6-week wash-out period, received a second mobilization therapy consisting of PlGF (130 μg/kg, IV, for 5 days) plus G-CSF (cycle 2). After an additional 6-week wash-out period, a third mobilization cycle consisting of PlGF (260 μg/kg, IV, for 5 days) plus G-CSF (cycle 3) was administered. Hematopoietic mobilization was evaluated by white blood cell counts (WBCs), committed colony-forming cells (CFCs), high-proliferative potential CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). Mobilization parameters were analyzed daily during treatment (days 1 to 5), and 3 and 5 days post-cessation of therapy. As compared to baseline values, a 5-day administration of G-CSF alone induced an average 5-fold increment of the mean (±SD) WBC counts (8,708±2,458 vs 43,523±13,790, P ≤.005). As compared to G-CSF alone, the peak values of WBCs were slightly increased by adding PlGF at 130 μg/kg (60,040±9,508) or 260 μg/kg (49,048±7,120). As compared to pretreatment values, the absolute numbers of circulating CFCs per ml blood were increased on average by 85-, 335-, and 358-fold under G-CSF (11,406±4,093, P ≤.005), G-CSF/PlGF 130 μg/kg (46,283±8,287, P ≤.005), and G-CSF/PlGF 260 μg/kg (60,777±8,563, P ≤.005), respectively. At cycles 2 and 3, the peak levels of CFCs were increased by 4- and 5-fold over cycle 1 (G-CSF alone). As compared to pretreatment values, the absolute numbers of circulating HPP-CFCs per ml blood were increase on average by 17-, 158, and 284-fold after under G-CSF (1,593±405, P ≤.005), G-CSF/PlGF 130 μg/kg (8,557±1,142, P ≤.005), and G-CSF/PlGF 260 μg/kg (12,205±2,172, P ≤.005), respectively. At cycles 2 and 3, the levels of day-5 HPP-CFCs were increased by 5- and 8-fold over cycle 1. Under G-CSF alone, the absolute numbers of circulating LTC-ICs were increased by 53-fold as compared to baseline values (211±41 vs 4±7, P≤.005). The combined G-CSF/PlGF (130 μg/kg) treatment increased LTC-ICs by 389-fold as compared to pretreatment values (3,115±988 vs 8±5, P≤.005), with a 15-fold increase over G-CSF alone. In conclusion, our data demonstrate that in nonhuman primates PlGF strongly synergizes with G-CSF for the mobilization of primitive and committed PBPCs.

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.

Suppression of Alkali Burn-Induced Corneal Neovascularization by Dendritic Cell Vaccination Targeting VEGF Receptor 2

2008 ◽  
Vol 49 (5) ◽  
pp. 2172 ◽  
Author(s):  
Hiroshi Mochimaru ◽  
Tomohiko Usui ◽  
Tomonori Yaguchi ◽  
Yasuharu Nagahama ◽  
Go Hasegawa ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Corneal Neovascularization ◽  
Dendritic Cell Vaccination ◽  
Vegf Receptor ◽  
Alkali Burn

scholarly journals Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

2015 ◽  
Vol 36 (3) ◽  
pp. 930-936 ◽  
Author(s):  
Hua Jiang ◽  
Xinyi Wu ◽  
Hong Wang ◽  
Chao Huang ◽  
Linna Zhang
Keyword(s):  
Growth Factor ◽  
Normal Tissue ◽  
Bioluminescence Imaging ◽  
Placental Growth Factor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Combined Treatments ◽  
Paired Normal Tissue ◽  
Endothelial Growth Factor ◽  
Cd31 Expression

Background/Aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH). So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A), or endostatin, do not always lead to satisfactory therapeutic outcome. Methods: We examined the VEGF receptor 1 (VEGFR1) levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression. Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF) may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect. Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.

scholarly journals Capillary Morphogenesis gene 2 mediates multiple pathways of growth factor-induced angiogenesis by regulating endothelial cell chemotaxis

2019 ◽  
Author(s):  
Lorna Cryan ◽  
Tsz-Ming Tsang ◽  
Jessica Stiles ◽  
Lauren Bazinet ◽  
Sai Lun Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Corneal Neovascularization ◽  
Tube Formation ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
The Novel ◽  
Capillary Morphogenesis ◽  
Pathological Angiogenesis ◽  
Endothelial Tube Formation ◽  
Endothelial Growth Factor

AbstractPathological angiogenesis contributes to diseases as varied as cancer and corneal neovascularization. The vascular endothelial growth factor (VEGF) - VEGF receptor 2 (KDR/VEGFR2) axis has been the major target for treating pathological angiogenesis. However, VEGF-targeted therapies exhibit reduced efficacy over time, indicating that new therapeutic strategies are needed. Therefore, identifying new targets that mediate angiogenesis is of great importance. Here, we report that one of the anthrax toxin receptors, capillary morphogenesis gene 2 (ANTXR2/CMG2), plays an important role in mediating angiogenesis induced by both bFGF and VEGF. Inhibiting physiological ligand binding to CMG2 results in significant reduction of corneal neovascularization, endothelial tube formation and cell migration. We also report the novel finding that CMG2 mediates angiogenesis by regulating the direction of endothelial chemotactic migration without affecting overall cell motility.

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.

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