scholarly journals Deficiency in the p110α subunit of PI3K results in diminished Tie2 expression and Tie2-/-–like vascular defects in mice

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3935-3938 ◽  
Author(s):  
Etienne Lelievre ◽  
Pierre-Marie Bourbon ◽  
Li-Juan Duan ◽  
Robert L. Nussbaum ◽  
Guo-Hua Fong
Keyword(s):  
Tyrosine Kinases ◽  
Branching Morphogenesis ◽  
Vascular Endothelial ◽  
Mouse Development ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

AbstractPhosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development. However, the in vivo role of PI3K during developmental vascularization remains to be defined. Here we demonstrate that mice deficient in the p110α catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced branching morphogenesis in the endocardium, lack of hierarchical order of large and small branches in the yolk sac, and impaired development of anterior cardinal veins. These vascular defects are strikingly similar to those in mice defective in the Tie2 signaling pathway. Indeed, Tie2 protein levels were significantly lower in p110α-deficient mice. Furthermore, RNA interference of p110α in cultured endothelial cells significantly reduced Tie2 protein levels. These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development.

scholarly journals Role of vascular endothelial growth factor in inducing production of angiopoetin-1 – in vivo study in Fisher rats

2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Study ◽  
Vascular Endothelial ◽  
Angiopoetin 1 ◽  
Endothelial Growth Factor

ACTH depletion represses vascular endothelial-cadherin transcription in mouse adrenal endothelium in vivo

2005 ◽  
Vol 34 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Philippe Huber ◽  
Christine Mallet ◽  
Elodie Faure ◽  
Christine Rampon ◽  
Marie-Hélène Prandini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial ◽  
Flow Cytometry Analysis ◽  
Adhesion Protein ◽  
Adrenal Cells ◽  
Protein Levels ◽  
Vascular Endothelial Cadherin ◽  
Complex Architecture

Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion protein that is localised at cell–cell contacts. This molecule is an important determinant of vascular architecture and endothelial cell survival. In the adrenal cortex, steroidogenic and endothelial cells form a complex architecture. The adrenocorticotrophin hormone (ACTH) regulates gland homeostasis whose secretion is subjected to a negative feedback by adrenocorticosteroids. The aim of the present study was to determine whether VE-cadherin expression in the adrenal gland was regulated by hormonal challenge. We demonstrated that VE-cadherin protein levels were dramatically decreased (23.5 ± 3.7%) by dexamethasone injections in the mouse and were restored by ACTH within 7 days (94.9 ± 18.6%). Flow cytometry analysis of adrenal cells showed that the ratios of endothelial versus total adrenal cells were identical (35%) in dexamethasone- or ACTH-treated or untreated mice, suggesting that VE-cadherin expression could be regulated by ACTH. We demonstrate the existence of a transcriptional regulation of the VE-cadherin gene using transgenic mice carrying the chloramphenicol acetyl transferase gene under the control of the VE-cadherin promoter. Indeed, the promoter activity in the adrenals, but not in the lung or liver, was decreased in response to dexamethasone treatment (40 ± 1.3%) and was partially restored after gland regeneration by ACTH injection (82 ± 3%). In conclusion, our results show that transcription of a specific endothelial gene is controlled by the hypothalamo–pituitary axis and the data expand the knowledge regarding the role of ACTH in the regulation of the adrenal vascular network.

scholarly journals Intervention Effect of Electroacupuncture Combined with EPCs Transplantation on the Mice in Aging Model

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Mei Wen
Keyword(s):  
Liver Tissue ◽  
Vascular Endothelial ◽  
Vascular Aging ◽  
Vascular Endothelial Function ◽  
Vegf Expression ◽  
Intervention Effect ◽  
Protein Levels ◽  
Tissue Fluorescence ◽  
Endothelial Growth Factor

The results of this experiment suggested that electroacupuncture promotes the endothelialization of liver endothelial progenitor cells (EPCs) for mice in D-gal model and improves the repair of vascular endothelial function, as well as increasing the vascular endothelial growth factor (VEGF) expression in liver tissue fluorescence and KL protein levels. Also, it reduces the malondialdehyde (MDA) activity and delays vascular aging and even overall aging. Results showed that the in vivo fluorescence intensity for D-gal EA group was significantly lower than that of D-gal group,P<0.05; VEGF fluorescence expression in liver tissue for D-gal EA group was significantly higher than that for D-gal group,P<0.05; KL protein content in liver tissue for D-gal EA group was significantly higher than that for D-gal group,P<0.05; MDA activity for D-gal EA group was significantly lower than that for D-gal group,P<0.05.

Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 638-645 ◽  
Author(s):  
Nicola Giuliani ◽  
Simona Colla ◽  
Mirca Lazzaretti ◽  
Roberto Sala ◽  
Giovanni Roti ◽  
...  
Keyword(s):  
Myeloma Cell ◽  
Vascular Endothelial ◽  
Myeloma Cells ◽  
Vessel Formation ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

AbstractPatients with multiple myeloma (MM) have increased bone marrow (BM) angiogenesis; however, the proangiogenic properties of myeloma cells and the mechanisms of MM-induced angiogenesis are not completely clarified. The angiopoietin system has been identified as critical in the regulation of vessel formation. In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels. In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells. Moreover, in an experimental model of angiogenesis, the conditioned medium of HMCLs significantly stimulated vessel formation compared with control or vascular endothelial growth factor (VEGF) treatment. The presence of anti-Tie2 blocking antibody completely blunted the proangiogenic effect of XG-6. Finally, our in vitro results were supported by the in vivo finding of Ang-1, but not Ang-2, mRNA and protein expression in purified MM cells obtained from approximately 47% of patients and by high BM angiogenesis in patients with MM positive for Ang-1, suggesting that the angiopoietin system could be involved, at least in part, in MM-induced angiogenesis.

Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation

2017 ◽  
Vol 29 (8) ◽  
pp. 1530 ◽  
Author(s):  
Jinhai Gou ◽  
Jia Jia ◽  
Juntao Feng ◽  
Xia Zhao ◽  
Tao Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Embryo Implantation ◽  
Hypoxia Inducible Factor ◽  
Implantation Site ◽  
Vascular Endothelial ◽  
Stathmin 1 ◽  
Endothelial Growth Factor

The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.

scholarly journals Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammation

2020 ◽  
Vol 26 (4) ◽  
pp. 240-255
Author(s):  
Yongpei He ◽  
Ting Xiong ◽  
Fang Guo ◽  
Zhenzhen Du ◽  
Yixian Fan ◽  
...  
Keyword(s):  
Early Stage ◽  
Inflammatory Factors ◽  
Epithelial Cell Line ◽  
Vascular Endothelial ◽  
Gynecological Disease ◽  
Endothelial Growth Factor ◽  
In Vitro Treatment

Abstract Endometriosis is a gynecological disease with abnormal expression of interleukin (IL)-37 which can suppress inflammation and the immune system. Here we investigated the role of the IL-37b splice variant in endometriosis in vivo and in vitro. In a murine model of endometriosis, in vivo administration of IL-37b significantly inhibited the development of lesions judged by the number (P = 0.0213), size (P = 0.0130) and weight (P = 0.0152) of lesions. IL-37b had no effect on the early stage of lesion formation, however administration in the growth stage of lesions decreased the number (P = 0.0158), size (P = 0.0158) and weight (P = 0.0258) of lesions compared with PBS control, an effect that was not reversed by macrophage depletion. Expressions of inflammatory factors, matrix metalloproteinases and vascular endothelial growth factor-A mRNA/protein were significantly inhibited in ectopic lesions following IL-37b administration, and in uterine segments treated in vitro. In vitro treatment of uterine segments with IL-37b inhibited phosphorylation of Akt and Erk1/2 in uterine segments. Isolated mouse endometrial stromal treated with IL-37b and transfected with pIL-37b plasmid got suppressed cell proliferation, invasion, angiogenesis and the expression of inflammatory factors. In addition, transfection with pIL-37b significantly decreased the phosphorylation of Akt and Erk1/2. IL-37b also inhibited proliferation and the expression of inflammatory and angiogenesis factors in epithelial cell line RL95–2. These findings suggest that IL-37b may inhibit the growth of lesions by regulating proliferation, invasion, angiogenesis and inflammation through Akt and Erk1/2 signaling pathway.

scholarly journals Blockade of in vivo VEGF-mediated angiogenesis by antisense gene therapy: role of Flk-1 and Flt-1 receptors

2002 ◽  
Vol 282 (1) ◽  
pp. H194-H204 ◽  
Author(s):  
Geneviève S. Marchand ◽  
Nicolas Noiseux ◽  
Jean-François Tanguay ◽  
Martin G. Sirois
Keyword(s):  
Blood Vessels ◽  
Fetal Liver ◽  
Capillary Blood ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Antisense Gene ◽  
Endothelial Growth Factor ◽  
Phosphate Buffered Saline

Angiogenesis, the formation of new blood vessels from preexisting ones, is a critical component of various pathologies such as tumor progression, rheumatoid arthritis, and retinopathies. Vascular endothelial growth factor (VEGF) is a mitogenic and chimiotactic factor capable of inducing angiogenesis through the activation of its receptors, fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), expressed on endothelial cells. The purpose of the present study was to assess if a treatment with antisense (AS) oligonucleotides directed against VEGF receptors Flk-1 or Flt-1 mRNA could prevent VEGF-mediated angiogenesis. With the use of miniosmotic pumps, phosphate-buffered saline, VEGF, or VEGF combined with AS-Flk-1, AS-Flt-1, or AS-scrambled oligonucleotides were released in mouse testis for 14 days. VEGF (1, 2.5, and 5 μg) increased the formation of new capillary blood vessels by 236, 246, and 287%, respectively. The combination of AS-Flk-1 or AS-Flt-1 (200 μg) to VEGF (2.5 μg) reduced by 87 and 85% the formation of new blood vessels, respectively, and the expression of their corresponding proteins. These data demonstrate the therapeutical potential of AS-Flk-1 or AS-Flt-1 to prevent VEGF-mediated angiogenesis in vivo.

scholarly journals Phytochemicals Targeting VEGF and VEGF-Related Multifactors as Anticancer Therapy

2019 ◽  
Vol 8 (3) ◽  
pp. 350 ◽  
Author(s):  
Amna Parveen ◽  
Lalita Subedi ◽  
Heung Kim ◽  
Zahra Khan ◽  
Zahra Zahra ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Anticancer Therapy ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Multiple Factors ◽  
Cancer Initiation ◽  
Bioactive Phytochemicals ◽  
Endothelial Growth Factor

The role of vascular endothelial growth factor (VEGF) in cancer cells is not limited to angiogenesis; there are also multiple factors, such as neuropilins (non-tyrosine kinases receptors), tyrosine kinases receptors, immunodeficiencies, and integrins, that interact with VEGF signaling and cause cancer initiation. By combating these factors, tumor progression can be inhibited or limited. Natural products are sources of several bioactive phytochemicals that can interact with VEGF-promoting factors and inhibit them through various signaling pathways, thereby inhibiting cancer growth. This review provides a deeper understanding of the relation and interaction of VEGF with cancer-promoting factors and phytochemicals in order to develop multi-targeted cancer prevention and treatment.

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