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

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 ◽

10.1182/blood-2002-10-3257 ◽

2003 ◽

Vol 102 (2) ◽

pp. 638-645 ◽

Cited By ~ 73

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.

Expression of vascular endothelial growth factor in response to high glucose in rat mesangial cells

Journal of Endocrinology ◽

10.1677/joe.0.1650617 ◽

2000 ◽

Vol 165 (3) ◽

pp. 617-624 ◽

Cited By ~ 53

Author(s):

NH Kim ◽

HH Jung ◽

DR Cha ◽

DS Choi

Keyword(s):

Diabetic Nephropathy ◽

Growth Factor ◽

High Glucose ◽

Mesangial Cells ◽

Vascular Endothelial ◽

Vegf Expression ◽

Protein Levels ◽

Calphostin C ◽

Diabetic nephropathy associated with hyperglycemia is characterized by glomerular hyperfiltration and endothelial dysfunction. Vascular endothelial growth factor (VEGF) is known to be primarily involved in neoangiogenesis and increased endothelial permeability. The purpose of this study was to investigate VEGF expression in response to high glucose in rat cultured mesangial cells and to identify its signal pathway via protein kinase C (PKC). Rat mesangial cells were cultured with different concentrations of glucose: normal (5 mM d-glucose), medium (15 mM d-glucose) and high (30 mm d-glucose). Calphostin-C as a PKC inhibitor and phorbol myristate acetate (PMA) as a PKC downregulator were instillated into culture media to evaluate the role of PKC in mediating the glucose-induced increase in VEGF expression. High glucose increased expression of VEGF at the mRNA and protein levels, identified by semi-quantitative RT-PCR and western blotting, within 3 h and in a time- and glucose concentration-dependent manner. Calphostin-C and PMA inhibited glucose-induced increases in VEGF expression at the mRNA and protein levels. In conclusion, high glucose can directly increase VEGF expression in rat mesangial cells via a PKC-dependent mechanism. These results suggest that VEGF could be a potential mediator of glomerular hyperfiltration and proteinuria in diabetic nephropathy.

Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo

Blood ◽

10.1182/blood.v96.12.3801.h8003801_3801_3808 ◽

2000 ◽

Vol 96 (12) ◽

pp. 3801-3808 ◽

Cited By ~ 2

Author(s):

Michael Melter ◽

Marlies E. J. Reinders ◽

Masayuki Sho ◽

Soumitro Pal ◽

Christopher Geehan ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Luciferase Reporter ◽

Ribonuclease Protection Assay ◽

Dependent Manner ◽

Vascular Endothelial ◽

Vegf Expression ◽

This study addresses a mechanism by which lymphocytes may promote vascular endothelial growth factor (VEGF) expression and angiogenesis in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA (mRNA) by reverse transcription polymerase chain reaction and ribonuclease protection assay with little or no change in expression following activation by cytokines, including tumor necrosis factor-α, interleukin (IL)–1, interferon γ, or IL-4. In contrast, treatment of HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a marked dose-dependent induction of VEGF mRNA (approximately 4-fold), which peaked between 1 and 5 hours post-stimulation. Transient transfection of HUVECs was performed with a luciferase reporter construct under the control of the human VEGF promoter. Treatment of transfected HUVECs with sCD40L was found to enhance luciferase activity (approximately 4-fold) compared with controls, similar to the relative fold induction in mRNA expression in parallel cultures. Thus, CD40-dependent VEGF expression was a result of transcriptional control mechanisms. Treatment of HUVECs with sCD40L was also found to function in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and nude mice induced VEGF expression and marked angiogenesis in vivo. Taken together, these findings are consistent with a function for CD40L-CD40 interactions in VEGF-induced angiogenesis and define a mechanistic link between the immune response and angiogenesis.

Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo

Blood ◽

10.1182/blood.v96.12.3801 ◽

2000 ◽

Vol 96 (12) ◽

pp. 3801-3808 ◽

Cited By ~ 129

Author(s):

Michael Melter ◽

Marlies E. J. Reinders ◽

Masayuki Sho ◽

Soumitro Pal ◽

Christopher Geehan ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Luciferase Reporter ◽

Ribonuclease Protection Assay ◽

Dependent Manner ◽

Vascular Endothelial ◽

Vegf Expression ◽

Abstract This study addresses a mechanism by which lymphocytes may promote vascular endothelial growth factor (VEGF) expression and angiogenesis in immune inflammation. Resting human umbilical endothelial cells (HUVECs) were found to express low levels of VEGF messenger RNA (mRNA) by reverse transcription polymerase chain reaction and ribonuclease protection assay with little or no change in expression following activation by cytokines, including tumor necrosis factor-α, interleukin (IL)–1, interferon γ, or IL-4. In contrast, treatment of HUVECs and monocytes with soluble CD40 ligand (sCD40L) resulted in a marked dose-dependent induction of VEGF mRNA (approximately 4-fold), which peaked between 1 and 5 hours post-stimulation. Transient transfection of HUVECs was performed with a luciferase reporter construct under the control of the human VEGF promoter. Treatment of transfected HUVECs with sCD40L was found to enhance luciferase activity (approximately 4-fold) compared with controls, similar to the relative fold induction in mRNA expression in parallel cultures. Thus, CD40-dependent VEGF expression was a result of transcriptional control mechanisms. Treatment of HUVECs with sCD40L was also found to function in vitro to promote growth and proliferation in a VEGF-dependent manner, and CD40-dependent HUVEC growth was comparable to that found following treatment with recombinant human VEGF. Furthermore, subcutaneous injection of sCD40L in severe combined immunodeficient and nude mice induced VEGF expression and marked angiogenesis in vivo. Taken together, these findings are consistent with a function for CD40L-CD40 interactions in VEGF-induced angiogenesis and define a mechanistic link between the immune response and angiogenesis.

Abstract 178: Angiogenesis is Triggered by Nutrient Deprivation via Gcn2/atf4-dependent Regulation of Vegf and H2s Production

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.178 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Alban Longchamp ◽

Teodelinda Mirabella ◽

Christopher Hine ◽

Lear E. Brace ◽

Nelson Knudsen ◽

...

Keyword(s):

Amino Acid ◽

Nutrient Sensing ◽

Nutrient Deprivation ◽

Vascular Endothelial ◽

Dietary Interventions ◽

Vegf Expression ◽

Eif2α Kinase ◽

Amino Acid Sensing ◽

Objective: Angiogenesis is crucial to maintain tissue homeostasis under nutrient and oxygen deprivation (ischemia). Although considerable evidence supports that angiogenesis is regulated by hypoxia-HIF1α induction of vascular endothelial growth factor (VEGF), the role of nutrient deprivation in angiogenesis is poorly defined. Approach and Results: We report that nutrient deprivation in the form of dietary sulfur amino acid restriction (Methionine/cysteine Restriction; MR) promotes VEGF expression and functional growth of new capillaries in skeletal muscle of mice (Fig.1 A, B). This occurred independently of hypoxia or HIF1α, but instead required the amino acid-sensing eIF2α kinase GCN2 and the transcription factor ATF4 (Fig. 1C). In addition to increased VEGF, nutrient deprivation boosted production of the pro-angiogenic gas hydrogen sulfide (H 2 S) via increased GCN2/ATF4-dependent expression of the H 2 S-generating enzyme cystathionine-gamma-lyase (CGL). The genetic requirement for CGL in angiogenesis triggered by nutrient deprivation, exercise or local VEGF overexpression, as well as the ability of local CGL overexpression to promote angiogenesis in vivo, revealed the critical importance of CGL-derived H 2 S in angiogenesis (Fig. 1D). Finally, plasma H 2 S was reduced in patients with vascular disease (versus non-diseased age-matched controls), and correlated with 2-year survival following vascular surgery (Fig.1 E, F). Conclusions: These data reveal a nutrient-sensing pathway targetable by diet as a previously unrecognized central regulator of VEGF expression and angiogenesis independent of canonical hypoxic signaling. This discovery points to novel dietary interventions and GCN2/ATF4/CGL/H 2 S-based strategies to manipulate angiogenesis. Figure 1

S1577 Endothelin Inhibits Both In Vivo and In Vitro Cholangiocarcinoma Growth By a Decrease in Vascular Endothelial Growth Factor (VEGF) Expression

Gastroenterology ◽

10.1016/s0016-5085(09)63767-7 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-817

Author(s):

Giammarco Fava ◽

Sharon DeMorrow ◽

Heather Francis ◽

Eugenio Gaudio ◽

Paolo Onori ◽

...

Keyword(s):

Growth Factor ◽

Vascular Endothelial ◽

Vegf Expression ◽

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

Blood ◽

10.1182/blood-2004-10-3955 ◽

2005 ◽

Vol 105 (10) ◽

pp. 3935-3938 ◽

Cited By ~ 36

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 ◽

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.

Inhibitory Effects of Doxycycline on Tumor Progression In vitro and on Metastases in Early-Stage Osteosarcoma Xenografts Mice.

10.21203/rs.3.rs-1019005/v2 ◽

2022 ◽

Author(s):

Argyris Costas Hadjimichael ◽

Athanasios F. Foukas ◽

Evangelia Papadimitriou ◽

Chrysostomi Peristiani ◽

Ioannis Chaniotakis ◽

...

Keyword(s):

Pulmonary Metastases ◽

Early Stage ◽

Vascular Endothelial ◽

Primary Tumors ◽

Protein Levels ◽

High Propensity ◽

And Migration ◽

Abstract Introduction. Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis, effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cells’ growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo. Methods. In vitro, the effect of Dox was measured in MG-63 and 143B human OS cells’ viability, apoptosis, and migration. In vivo, highly metastatic143B cells were orthotopically implanted into the tibia of SCID mice and tumor growth as well as pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined. Results. Dox decreased the viability, inhibited the migration, and induced the apoptosis of OS cells in vitro. In vivo, Dox significantly enhanced tumor necrosis at primary OS sites, similarly to its in vitro effect. It also decreased the expression of Ki67, metalloproteinases 2 and 9 (MMP2 and MMP9), vascular endothelial growth factor A (VEGFA) and Ezrin in primary tumors. It also decreased the circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice in both non-amputated and early amputated xenografts. Conclusions. Our results suggest that adjuvant administration of Dox may decrease OS growth and development of pulmonary metastases. Administration of Dox in combination with surgical resection and standard chemotherapeutic protocols in the early-stages of OS treatment is also supported. Moreover, Dox administration prior to the development of clinically detectable pulmonary macrometastases, is associated with enhanced clinically benefits from its anti-metastatic effect.

The Antiangiogenic Effect of Sanguinarine Chloride on Experimental Choroidal Neovacularization in Mice via Inhibiting Vascular Endothelial Growth Factor

Frontiers in Pharmacology ◽

10.3389/fphar.2021.638215 ◽

2021 ◽

Vol 12 ◽

Author(s):

Junxiu Zhang ◽

Ke Mao ◽

Qing Gu ◽

Xingwei Wu

Keyword(s):

Growth Factor ◽

Tube Formation ◽

Vascular Endothelial ◽

Vegf Expression ◽

Antiangiogenic Effect ◽

Laser Injury ◽

Background: The purpose of this study is to investigate the antiangiogenic effect of Sanguinarine chloride (SC) on models of age-related macular degeneration (AMD) both in vivo and in vitro.Methods: Choroidal neovascularization (CNV) was conducted by laser photocoagulation in C57BL6/J mice. SC (2.5 μM, 2 μl/eye) was intravitreally injected immediately after laser injury. The control group received an equal amount of PBS. 7 days after laser injury, CNV severity was evaluated using fundus fluorescein angiography, hematoxylin and eosin (H&E) staining, and choroid flat-mount staining. Vascular endothelial growth factor (VEGF) expression in the retina/choroid complex was measured by western blot analysis and ELISA kit. In vitro, human retinal microvascular endothelial cells (HRMECs) were used to investigate the effects of SC on cell tube formation, migration, and cytotoxicity. The expression of VEGF-induced expression of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (AKT), mitogen-activated protein kinases (p38-MAPK) in vitro and laser induced VEGF expression in vivo were also analyzed.Results: SC (≤2.5 μM) was safe both in vitro and in vivo. Intravitreal injection of SC restrained the formation of laser induced CNV in mice and decreased VEGF expression in the laser site of the retina/choroid complex. In vitro, SC inhibited VEGF-induced tube formation and endothelial cell migration by decreasing the phosphorylation of AKT, ERK1/2, and p38-MAPK in HRMECs.Conclusions: SC could inhibit laser-induced CNV formation via down-regulating VEGF expression and restrain the VEGF-induced tube formation and endothelial migration. Therefore, SC could be a potential candidate for the treatment of wet AMD.