scholarly journals Monocyte activation state regulates monocyte-induced endothelial proliferation through Met signaling

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3407-3412 ◽  
Author(s):  
Shai Y. Schubert ◽  
Alejandro Benarroch ◽  
Juan Monter-Solans ◽  
Elazer R. Edelman
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Direct Interaction ◽  
Endothelial Cell Proliferation ◽  
Specific Cell ◽  
Mrna Levels ◽  
Hepatocyte Growth

Abstract Direct interaction of unactivated primary monocytes with endothelial cells induces a mitogenic effect in subconfluent, injured endothelial monolayers through activation of endothelial Met. We now report that monocytes' contact-dependent mitogenicity is controlled by activation-mediated regulation of hepatocyte growth factor. Direct interaction of unactivated monocytes with subconfluent endothelial cells for 12 hours resulted in 9- and 120-fold increase in monocyte tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) mRNA levels and bitemporal spike in hepatocyte growth factor that closely correlates with endothelial Met and extracellular signal-related kinase (ERK) phosphorylation. Once activated, monocytes cannot induce a second wave of endothelial cell proliferation and endothelial Met phosphorylation and soluble hepatocyte growth factor levels fall off. Monocyte-induced proliferation is dose dependent and limited to the induction of a single cell cycle. Monocytes retain their ability to activate other endothelial cells for up to 8 hours after initial interaction, after which they are committed to the specific cell. There is therefore a profoundly sophisticated mode of vascular repair. Confluent endothelial cells ensure vascular quiescence, whereas subconfluence promotes vessel activation. Simultaneously, circulating monocytes stimulate endothelial cell proliferation, but lose this potential once activated. Such a system provides for the fine balance that can restore vascular and endothelial homeostasis with minimal overcompensation.

W03-P-007 Hepatocyte growth factor-induced signaling in endothelial cell proliferation

2005 ◽  
Vol 6 (1) ◽  
pp. 14
Author(s):  
C.R.W. Kuhlmann ◽  
A. Fehsecke ◽  
C.A. Schaefer ◽  
A.K. Most ◽  
H. Tillmanns ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Endothelial Cell Proliferation ◽  
Hepatocyte Growth

Proliferation of endothelial cells in neoangiogenesis of human cortical glioblastoma

2008 ◽  
Vol 3 (2) ◽  
pp. 113-119
Author(s):  
Mira Krstulja ◽  
David Bonifacic ◽  
Slobodan Cvejanović
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunohistochemical Staining ◽  
Endothelial Cell Proliferation ◽  
Specific Cell ◽  
Medical Doctors ◽  
Close Proximity ◽  
Double Immunohistochemical Staining ◽  
First Time

AbstractIn 1982 Vilanova et al. quantitatively described the neovessel area in glioblastoma and suggested zonal differences in vessel surface area. In this study we investigated specific cell proliferation and angiogenic patterns in the vessel compartment of cortical glioblastoma. We used Ki67, CD34 and SMA double immunohistochemical staining to quantitate vascular patterns and cell specific proliferation and presented glioblastoma with several parameters of angiogenesis. Endothelial cell proliferation was higher in complex and bizzare neovessels than in the simple and sprouting glioblastoma neovessels. There was a higher frequency of sprouting simple vessels in close proximity to the palisade and a higher frequency of bizzare vessels in the microzone distant to the palisade. Quantitatively presented for the first time, the neovessel proliferation patterns support cortical glioblastoma compartmentalization. The data obtained are relevant to medical doctors using neoangiogenesis in diagnosis, prognosis and therapy of neoplasia. The results obtained in 15 patients call for further investigation of endothelial cell/pericyte relationships and glioblastoma compartmentalization.

scholarly journals Vascular Endothelial Growth Factor Mediates the Estrogen-Induced Breakdown of Tight Junctions between and Increase in Proliferation of Microvessel Endothelial Cells in the Baboon Endometrium

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6076-6083 ◽  
Author(s):  
Graham W. Aberdeen ◽  
Stanley J. Wiegand ◽  
Thomas W. Bonagura ◽  
Gerald J. Pepe ◽  
Eugene D. Albrecht
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Tight Junctions ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Vegf Trap

To assess whether there is a link between estrogen, vascular endothelial growth factor (VEGF), and early aspects of uterine angiogenesis, an acute temporal study was conducted in which ovariectomized baboons were pretreated with VEGF Trap, which sequesters endogenous VEGF, and administered estradiol at time 0 h. Serum estradiol levels approximated 500 pg/ml 4–6 h after estradiol administration. VEGF mRNA levels in endometrial glandular epithelial and stromal cells were increased to values 6 h after estradiol that were 3.74 ± 0.99-fold (mean ± se) and 5.70 ± 1.60-fold greater (P < 0.05), respectively, than at 0 h. Microvessel interendothelial cell tight junctions, which control paracellular permeability, were present in the endometrium at time 0 h, but not evident 6 h after estradiol administration. Thus, microvessel paracellular cleft width increased (P < 0.01, ANOVA) from 5.03 ± 0.22 nm at 0 h to 7.27 ± 0.48 nm 6 h after estrogen. In contrast, tight junctions remained intact, and paracellular cleft widths were unaltered in estradiol/VEGF Trap and vehicle-treated animals. Endometrial microvessel endothelial cell mitosis, i.e. percent Ki67+/Ki67− immunolabeled endothelial cells, increased (P < 0.05) from 2.9 ± 0.3% at 0 h to 21.4 ± 7.0% 6 h after estrogen treatment but was unchanged in estradiol/VEGF Trap and vehicle-treated animals. In summary, the estrogen-induced disruption of endometrial microvessel endothelial tight junctions and increase in endothelial cell proliferation were prevented by VEGF Trap. Therefore, we propose that VEGF mediates the estrogen-induced increase in microvessel permeability and endothelial cell proliferation as early steps in angiogenesis in the primate endometrium.

scholarly journals Thrombospondin-4 (TSP4) gene-modified bone marrow stromal cells (BMSCs) promote the effect of therapeutic angiogenesis in critical limb ischemia (CLI) of diabetic rats

2019 ◽  
Author(s):  
Qian Zhang ◽  
Tao Wang ◽  
Xiangfeng Wu ◽  
Ying Wang ◽  
Xuanqin Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Motor Function ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Thrombospondin 4

Abstract Background: Critical limb ischemia (CLI) is the leading cause of lower limb amputation. Traditional treatments for CLI have limitations. Studies have shown that thrombospondin-4 (TSP4) can promote the growth of neovascularization. Results: In this study, we observed the angiogenesis efficiency of TSP4-overexpressing BMSC transplantation in CLI treatment. The recombinant FT106-tsp4-gfp lentiviral vector plasmid was constructed and transfected into 293FT cells. Primary BMSCs were successfully infected with the tsp4 virus, and TSP4 overexpression was confirmed before TSP4-BMSCs infusion. In vitro, TSP4-BMSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) secretion were measured in the co-culture supernatants by ELISA. The effect of TSP4-BMSCs on endothelial cell proliferation and migration was detected. Meanwhile, the effects of TSP4-BMSC on the angiogenesis of endothelial cells were tested by tube formation experiment and arterial ring test. In vivo, a rat CLI model was established, and 60 CLI rats were randomly divided into the CLI, BMSC + CLI and TSP4-BMSC + CLI groups. The effect of TSP4-BMSC on angiogenesis was detected by the motor function, immunohistochemistry and immunofluorescence staining assays. Neovascular density was detected by digital substraction angiography (DSA). Our results demonstrated that TSP4-BMSCs obviously increased TSP4, VEGF, Ang-1, MMP9, MMP2 and p-Cdc42/Rac1 expression in endothelial cells. TSP4-BMSCs treatment notably upregulated the TGF-β/smad2/3 signal pathway in HUVECs. In vivo, TSP4-BMSCs improved the motor function score of the CLI rats and increased MMP2, MMP9, Ang-1, VEGF and vWF protein expression in tissue of the ischaemic area. Meanwhile, new blood vessels can be observed around the ischemic area after TSP4-BMSCs treatment. Conclusion: Our data illustrate that TSP4-BMSCs can promote endothelial cell proliferation, migration, tube formation and the recovery of motor function in diabetic hind limb ischaemic rats. TSP4-BMSCs have better therapeutic effects than BMSCs.

scholarly journals Thrombospondin-4 (TSP4) gene-modified bone marrow stromal cells (BMSCs) promote the effect of therapeutic angiogenesis in critical limb ischemia (CLI) of diabetic rats

2020 ◽  
Author(s):  
Qian Zhang ◽  
Tao Wang ◽  
Xiangfeng Wu ◽  
Ying Wang ◽  
Xuanqin Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Motor Function ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Thrombospondin 4

Abstract Background Critical limb ischemia (CLI) is the leading cause of lower limb amputation. Traditional treatments for CLI have limitations. Studies have shown that thrombospondin-4 (TSP4) can promote the growth of neovascularization. In this study, we observed the angiogenesis efficiency of TSP4-overexpressing BMSC transplantation in CLI treatment. Methods The recombinant FT106-tsp4-gfp lentiviral vector plasmid was constructed and transfected into 293FT cells. Primary BMSCs were successfully infected with the tsp4 virus, and TSP4 overexpression was confirmed before TSP4-BMSCs infusion. In vitro, TSP4-BMSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) secretion were measured in the co-culture supernatants by ELISA. The effect of TSP4-BMSCs on endothelial cell proliferation and migration was detected. Meanwhile, the effects of TSP4-BMSC on the angiogenesis of endothelial cells were tested by tube formation experiment and arterial ring test. In vivo, a rat CLI model was established, and 60 CLI rats were randomly divided into the CLI, BMSC + CLI and TSP4-BMSC + CLI groups. The effect of TSP4-BMSC on angiogenesis was detected by the motor function, immunohistochemistry and immunofluorescence staining assays. Neovascular density was detected by digital substraction angiography (DSA). Results Our results demonstrated that TSP4-BMSCs obviously increased TSP4, VEGF, Ang-1, MMP9, MMP2 and p-Cdc42/Rac1 expression in endothelial cells. TSP4-BMSCs treatment notably upregulated the TGF-β/smad2/3 signal pathway in HUVECs. In vivo, TSP4-BMSCs improved the motor function score of the CLI rats and increased MMP2, MMP9, Ang-1, VEGF and vWF protein expression in tissue of the ischaemic area. Meanwhile, new blood vessels can be observed around the ischemic area after TSP4-BMSCs treatment. Conclusions Our data illustrate that TSP4-BMSCs can promote endothelial cell proliferation, migration, tube formation and the recovery of motor function in diabetic hind limb ischaemic rats. TSP4-BMSCs have better therapeutic effects than BMSCs.

scholarly journals Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth.

1992 ◽  
Vol 119 (3) ◽  
pp. 629-641 ◽  
Author(s):  
F Bussolino ◽  
M F Di Renzo ◽  
M Ziche ◽  
E Bocchietto ◽  
M Olivero ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Monolayer ◽  
Angiogenic Factor ◽  
Tyrosine Kinase Receptor ◽  
Collagen Gels ◽  
Hepatocyte Growth

Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by the MET protooncogene. Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to endothelial cells identifies two sites with different affinities. The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub-nanomolar concentrations of HGF, but not of a recombinant inactive precursor, stimulate the receptor kinase activity, cell proliferation and motility. HGF induces repairs of a wound in endothelial cell monolayer. HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. In the rabbit cornea, highly purified HGF promotes neovascularization at sub-nanomolar concentrations. HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. These data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate.

scholarly journals Inhibition of endothelial cell proliferation by gamma-interferon.

1987 ◽  
Vol 104 (3) ◽  
pp. 689-696 ◽  
Author(s):  
R Friesel ◽  
A Komoriya ◽  
T Maciag
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Gamma Interferon ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Ligand Complex ◽  
Receptor Modulation

Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen for endothelial cells and fibroblasts. The mitogenic effects of ECGF are inhibited by the lymphokine gamma-interferon (gamma-IFN) in a dose-dependent manner. Gamma-IFN also induces a unique change in endothelial cell morphology which is maximally expressed in the presence of ECGF. The antiproliferative and phenotypic modulatory effects of gamma-IFN on endothelial cells are reversible. Inhibition of ECGF-induced endothelial cell proliferation by gamma-IFN is accompanied by a concentration- and time-dependent decrease in binding of 125I-ECGF to the endothelial cell surface. Scatchard analyses of the binding data in the presence and absence of gamma-IFN demonstrate a decrease in the number of ECGF-binding sites rather than a decrease in ligand affinity for the receptor. Cross-linking experiments with disuccinimidyl suberate demonstrate a decrease in the 170,000 Mr cross-linked receptor-ligand complex. These data suggest that gamma-IFN inhibits endothelial cell proliferation by a mechanism which involves growth factor receptor modulation.

Regulation of bovine glomerular endothelial cell growth in vitro

1989 ◽  
Vol 256 (1) ◽  
pp. C182-C189 ◽  
Author(s):  
B. J. Ballermann
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Endothelial Cell Proliferation ◽  
Fibroblast Growth ◽  
Glomerular Endothelial Cell ◽  
Glomerular Endothelial Cells ◽  
Endothelial Cell Growth

To enable the study of glomerular endothelial cell functions and interactions with other glomerular cells, bovine glomerular capillary endothelial cells were established in culture. Selective media were used to facilitate endothelial cell proliferation and to suppress glomerular mesangial cell growth. Glomerular endothelial cells were separated from other cell types by fluorescence-activated cell sorting or, alternatively, by cloning. Glomerular endothelial cells expressed angiotensin I-converting enzyme and factor VIII activity and acetylated LDL uptake, properties generally held to be specific for endothelial cells. Proliferation of subconfluent glomerular endothelial cells was stimulated by basic fibroblast growth factor and, in the presence of heparin sodium, by acidic fibroblast growth factor. Platelet-derived growth factor was without effect on glomerular endothelial cell proliferation. Coculture with mesangial cells markedly inhibited proliferation of subconfluent glomerular endothelial cells. By contrast, medium conditioned by confluent glomerular endothelial cells markedly enhanced proliferation of subconfluent glomerular endothelial cells. These findings suggest that glomerular endothelial cell growth is under autocrine and paracrine control.

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