scholarly journals Kisspeptin-10 inhibits OHSS by suppressing VEGF secretion

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Junyu Zhai ◽  
Jiansheng Liu ◽  
Shigang Zhao ◽  
Han Zhao ◽  
Zi-Jiang Chen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Granulosa Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Rat Models ◽  
Systemic Disorder ◽  
Main Regulator ◽  
Umbilical Vein Endothelial Cells ◽  
High Level ◽  
Endothelial Growth Factor

The aim of the present study was to elucidate the effects of kisspeptin-10 (Kp-10) on ovarian hyperstimulation syndrome (OHSS) and its related mechanism in OHSS rat models, human umbilical vein endothelial cells (HUVECs) and human luteinized granulosa cells. OHSS is a systemic disorder with high vascular permeability (VP) and ovarian enlargement. KISS1R (KISS1 receptor) is the specific receptor of kisspeptin. The kisspeptin/KISS1R system inhibits the expression of vascular endothelial growth factor (VEGF), which is the main regulator of VP. In our study, decreased expression of Kiss1r was observed in both ovaries and lung tissue of OHSS rats. Injection of exogenous Kp-10 inhibited the increase of VP and VEGF while promoting the expression of Kiss1r in both the ovarian and lung tissue of OHSS rats. Using HUVECs, we revealed that a high level of 17-β estradiol (E2), a feature of OHSS, suppressed the expression of KISS1R and increased VEGF and nitric oxide (NO) through estrogen receptors (ESR2). Furthermore, KISS1R mRNA also decreased in the luteinized human granulosa cells of high-risk OHSS patients, and was consistent with the results in rat models and HUVECs. In conclusion, Kp-10 prevents the increased VP of OHSS by the activation of KISS1R and the inhibition of VEGF.

Vascular endothelial growth factor–stimulated endothelial cells promote adhesion and activation of platelets

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4216-4221 ◽  
Author(s):  
Henk M. W. Verheul ◽  
Anita S. Jorna ◽  
Klaas Hoekman ◽  
Henk J. Broxterman ◽  
Martijn F. B. G. Gebbink ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
High Affinity Binding Site ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

Abstract Coagulation abnormalities, including an increased platelet turnover, are frequently found in patients with cancer. Because platelets secrete angiogenic factors on activation, this study tested the hypothesis that platelets contribute to angiogenesis. Stimulation with vascular endothelial growth factor (VEGF, 25 ng/mL) of human umbilical vein endothelial cells (HUVECs) promoted adhesion of nonactivated platelets 2.5-fold. In contrast, stimulation of HUVECs with basic fibroblast growth factor (bFGF) did not promote platelet adhesion. By blocking tissue factor (TF) activity, platelet adhesion was prevented and antibodies against fibrin(ogen) and the platelet-specific integrin, αIIbβ3, inhibited platelet adhesion for 70% to 90%. These results indicate that VEGF-induced platelet adhesion to endothelial cells is dependent on activation of TF. The involvement of fibrin(ogen) and the αIIbβ3 integrin, which exposes a high-affinity binding site for fibrin(ogen) on platelet activation, indicates that these adhering platelets are activated. This was supported by the finding that the activity of thrombin, a product of TF-activated coagulation and a potent platelet activator, was required for platelet adhesion. Finally, platelets at physiologic concentrations stimulated proliferation of HUVECs, indicative of proangiogenic activity in vivo. These results support the hypothesis that platelets contribute to tumor-induced angiogenesis. In addition, they may explain the clinical observation of an increased platelet turnover in cancer patients. Platelets may also play an important role in other angiogenesis-dependent diseases in which VEGF is involved, such as diabetes and autoimmune diseases.

scholarly journals Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions

2007 ◽  
Vol 28 (5) ◽  
pp. 1657-1668 ◽  
Author(s):  
Stéphanie Heyraud ◽  
Michel Jaquinod ◽  
Claire Durmort ◽  
Emilie Dambroise ◽  
Evelyne Concord ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Adherens Junctions ◽  
Lateral Diffusion ◽  
Cell Contact ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Annexin 2 ◽  
Umbilical Vein Endothelial Cells ◽  
Interfering Rna ◽  
Endothelial Growth Factor

ABSTRACT The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.

scholarly journals ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer

2018 ◽  
Vol 96 (6) ◽  
pp. 761-768 ◽  
Author(s):  
Sen Hong ◽  
Si Chen ◽  
Xu Wang ◽  
Di Sun ◽  
Zhenkun Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3′-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.

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