scholarly journals Production of a heparin-binding angiogenesis factor by the embryonic kidney.

1986 ◽  
Vol 103 (3) ◽  
pp. 1101-1107 ◽  
Author(s):  
W Risau ◽  
P Ekblom
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Blood Vessels ◽  
Gel Filtration ◽  
Chorioallantoic Membrane ◽  
Heparin Binding ◽  
Rabbit Cornea ◽  
Embryonic Mouse ◽  
Angiogenesis Factor

Embryonic mouse kidneys induce angiogenesis when transplanted on the quail chorioallantoic membrane (Ekblom, P., H. Sariola, M. Karkinen, and L. Saxén, 1982, Cell Differ., 11:35-39). In these experiments all blood vessels were derived from the quail host, suggesting that kidney endothelium is derived from outside blood vessels. We have now analyzed whether kidney angiogenesis is regulated by kidney-derived soluble factors that stimulate the growth of new blood vessels. In the rabbit cornea, 11-d embryonic kidneys induced angiogenesis, whereas uninduced 11-d kidney mesenchymes did not. To characterize and purify this activity from an embryonic organ, we dissected between 600 and 1,000 14-17-d-old embryonic mouse kidneys for each purification experiment. Growth factor activity for capillary endothelial cells was found to bind to heparin-Sepharose and eluted at 0.9-1.1 M sodium chloride. Gel filtration revealed a molecular weight of 16,000-20,000 of this factor. A major 18,000-mol-wt band was seen after gel electrophoresis and silver staining of partially purified growth factor material. The chromatographed factor is mitogenic for endothelial cells but not for smooth muscle cells and stimulates angiogenesis in vivo in the rabbit cornea. Adult kidneys contained two heparin-binding endothelial cell growth factors. The differentiation-dependent production of an angiogenesis factor by the embryonic kidney suggests an important role of angiogenesis in organogenesis.

I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4039-4045
Author(s):  
Giovanni Bernardini ◽  
Gaia Spinetti ◽  
Domenico Ribatti ◽  
Grazia Camarda ◽  
Lucia Morbidelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Rnase Protection Assay ◽  
Chorioallantoic Membrane ◽  
Rnase Protection ◽  
Cc Chemokine ◽  
Cell Functions

Several chemokines have been shown to act as angiogenic molecules or to modulate the activity of growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF). The detection of the CC chemokine receptor (CCR) 8 message in human umbilical vein endothelial cells (HUVECs) by reverse transcription– polymerase chain reaction (RT-PCR) and RNase protection assay (RPA), prompted us to investigate the potential role exerted by the CC chemokine I-309, a known ligand of such receptor, in both in vitro and in vivo angiogenesis assays. We show here that I-309 binds to endothelial cells, stimulates chemotaxis and invasion of these cells, and enhances HUVEC differentiation into capillary-like structures in an in vitro Matrigel assay. Furthermore, I-309 is an inducer of angiogenesis in vivo in both the rabbit cornea and the chick chorioallantoic membrane assay (CAM).

I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4039-4045 ◽  
Author(s):  
Giovanni Bernardini ◽  
Gaia Spinetti ◽  
Domenico Ribatti ◽  
Grazia Camarda ◽  
Lucia Morbidelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Rnase Protection Assay ◽  
Chorioallantoic Membrane ◽  
Rnase Protection ◽  
Cc Chemokine ◽  
Cell Functions

Abstract Several chemokines have been shown to act as angiogenic molecules or to modulate the activity of growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF). The detection of the CC chemokine receptor (CCR) 8 message in human umbilical vein endothelial cells (HUVECs) by reverse transcription– polymerase chain reaction (RT-PCR) and RNase protection assay (RPA), prompted us to investigate the potential role exerted by the CC chemokine I-309, a known ligand of such receptor, in both in vitro and in vivo angiogenesis assays. We show here that I-309 binds to endothelial cells, stimulates chemotaxis and invasion of these cells, and enhances HUVEC differentiation into capillary-like structures in an in vitro Matrigel assay. Furthermore, I-309 is an inducer of angiogenesis in vivo in both the rabbit cornea and the chick chorioallantoic membrane assay (CAM).

Kallistatin is a new inhibitor of angiogenesis and tumor growth

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3245-3252 ◽  
Author(s):  
Robert Q. Miao ◽  
Jun Agata ◽  
Lee Chao ◽  
Julie Chao
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Gene Delivery ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Vascular Function ◽  
Hind Limb ◽  
Heparin Binding

Abstract Kallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)– or basic fibroblast growth factor (bFGF)–induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth.

Capillary endothelial cells secrete a heparin-binding mitogen for pericytes

1992 ◽  
Vol 103 (2) ◽  
pp. 453-461
Author(s):  
J.C. Swinscoe ◽  
E.C. Carlson
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Acidic Fibroblast Growth Factor ◽  
Phenotypic Characteristics ◽  
Retinal Microvasculature ◽  
Capillary Endothelial Cells

The cells of the retinal microvasculature consist predominantly of mesodermally derived pericytes and endothelial cells, and the regulatory factors which govern their co-ordinated growth and define their phenotypic characteristics in vivo may be regarded as key elements of the angiogenic process. An investigation of these cells in co-culture experiments has led to the identification of a potent mitogen for pericytes in medium conditioned by retinal endothelial cells (EC-FBS). EC-FBS activity was shown to be non-dialyzable, and stable to both heat and acid treatment. EC-FBS was inactivated by passage over a heparin-Agarose column. The column-bound activity could be eluted as a single peak at approximately 1.0 M NaCl. Stimulation of pericyte growth was also achieved with platelet-derived growth factor (PDGF), acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) and could be blocked by using the appropriate antiserum (anti-PDGF or anti-aFGF). Neither antisera, however, blocked the activity of EC-FBS. The EC-FBS mitogen markedly altered the phenotypic behavior of pericytes compared with PDGF and the FGFs; yet, unlike them, it failed to stimulate the growth of smooth muscle cells (SMC) and Balb/c 3T3 cells.

scholarly journals Oncodevelopmental α-Fetoprotein Acts as a Selective Proangiogenic Factor on Endothelial Cell from the Fetomaternal Unit

2004 ◽  
Vol 89 (3) ◽  
pp. 1415-1422 ◽  
Author(s):  
Olin D. Liang ◽  
Thomas Korff ◽  
Jessica Eckhardt ◽  
Jasmin Rifaat ◽  
Nelli Baal ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Chorioallantoic Membrane ◽  
Protein S ◽  
First Trimester ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract The molecular coordination between angiogenesis and vascular remodeling is a critical step for the development of a functional vasculature in the placenta and the uterus during pregnancy. The oncodevelopmental albumin homolog α-fetoprotein (AFP) is mainly synthesized in the developing fetus, and its expression has been found to be associated with highly vascularized tumors in the adult. In this study, we investigated the angiogenic activity of AFP and its possible role in the fetomaternal unit. Immunohistochemical studies revealed that the AFP-binding protein(s) is expressed in blood vessels of chorionic villi from placentae of the second and the third but not of the first trimester during pregnancy. At low concentrations, AFP directly stimulates or enhances, respectively, vascular endothelial growth factor-induced proliferation and sprout formation of endothelial cells isolated from the placenta and the uterus possibly by a MAPK-dependent pathway. Furthermore, AFP enhances blood vessel formation in a chick chorioallantoic membrane assay in vivo. Interestingly, AFP has no proliferative or migratory effects on endothelial cells isolated from the umbilical vein in the absence of vascular endothelial growth factor. These data indicate that AFP may act as a specific proangiogenic factor of endothelial cells within the fetomaternal unit during advanced stages in pregnancy.

scholarly journals p38 MAP kinase negatively regulates endothelial cell survival, proliferation, and differentiation in FGF-2–stimulated angiogenesis

2002 ◽  
Vol 156 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Taro Matsumoto ◽  
Ingela Turesson ◽  
Majlis Book ◽  
Pär Gerwins ◽  
Lena Claesson-Welsh
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Chorioallantoic Membrane ◽  
Collagen Gel ◽  
P38 Map Kinase ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Chick Chorioallantoic Membrane

The p38 mitogen–activated protein kinase (p38) is activated in response to environmental stress and inflammatory cytokines. Although several growth factors, including fibroblast growth factor (FGF)-2, mediate activation of p38, the consequences for growth factor–dependent cellular functions have not been well defined. We investigated the role of p38 activation in FGF-2–induced angiogenesis. In collagen gel cultures, bovine capillary endothelial cells formed tubular growth-arrested structures in response to FGF-2. In these collagen gel cultures, p38 activation was induced more potently by FGF-2 treatment compared with that in proliferating cultures. Treatment with the p38 inhibitor SB202190 enhanced FGF-2–induced tubular morphogenesis by decreasing apoptosis, increasing DNA synthesis and cell proliferation, and enhancing the kinetics of cell differentiation including increased expression of the Notch ligand Jagged1. Overexpression of dominant negative mutants of the p38-activating kinases MKK3 and MKK6 also supported FGF-2–induced tubular morphogenesis. Sustained activation of p38 by FGF-2 was identified in vascular endothelial cells in vivo in the chick chorioallantoic membrane (CAM). SB202190 treatment enhanced FGF-2–induced neovascularization in the CAM, but the vessels displayed abnormal features indicative of hyperplasia of endothelial cells. These results implicate p38 in organization of new vessels and suggest that p38 is an essential regulator of FGF-2–driven angiogenesis.

scholarly journals Expression of SPARC during development of the chicken chorioallantoic membrane: evidence for regulated proteolysis in vivo.

1995 ◽  
Vol 6 (3) ◽  
pp. 327-343 ◽  
Author(s):  
M L Iruela-Arispe ◽  
T F Lane ◽  
D Redmond ◽  
M Reilly ◽  
R P Bolender ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Chorioallantoic Membrane ◽  
Focal Adhesions ◽  
Protein Accumulation ◽  
Dependent Manner ◽  
Plasmin Activity ◽  
Specific Expression ◽  
Chicken Chorioallantoic Membrane

SPARC is a secreted glycoprotein that has been shown to disrupt focal adhesions and to regulate the proliferation of endothelial cells in vitro. Moreover, peptides resulting from the proteolysis of SPARC exhibit angiogenic activity. Here we describe the temporal synthesis, turnover, and angiogenic potential of SPARC in the chicken chorioallantoic membrane. Confocal immunofluorescence microscopy revealed specific expression of SPARC protein in endothelial cells, and significantly higher levels of SPARC were observed in smaller newly formed blood vessels in comparison to larger, developmentally older vessels. SPARC mRNA was detected at the earliest stages of chorioallantoic membrane morphogenesis and reached maximal levels at day 13 of embryonic development. Interestingly, steady-state levels of SPARC mRNA did not correlate directly with protein accumulation; moreover, the protein appeared to undergo limited degradation during days 10-15. Incubation of [125I]-SPARC with chorioallantoic membranes of different developmental ages confirmed that extracellular proteolysis occurred during days 9-15, but not at later stages (e.g., days 17-21). Comparison of peptides produced by incubation with chorioallantoic membranes with those generated by plasmin showed an identical pattern of proteolysis. Plasmin activity was present throughout development, and in situ zymography identified sites of plasminogen activator activity that corresponded to areas exhibiting high levels of SPARC expression. Synthetic peptides from a plasmin-sensitive region of SPARC, between amino acids 113-130, stimulated angiogenesis in the chorioallantoic membrane in a dose-dependent manner; in contrast, intact SPARC was inactive in similar assays. We have shown that SPARC is expressed in endothelial cells of newly formed blood vessels in a manner that is both temporally and spatially restricted. Between days 9 and 15 of chorioallantoic membrane development, the protein undergoes proteolytic cleavage that is mediated, in part, by plasmin. SPARC peptides released specifically by plasmin induce angiogenesis in vivo. We therefore propose that SPARC acts as an intrinsic regulator of angiogenesis in vivo.

Suppression of Angiogenesis and Resistance to Doxorubicin by the Thyroid Hormone Tetraiodothyroacetic Acid.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4209-4209
Author(s):  
Shaker A. Mousa ◽  
Laura O’Connor ◽  
Ahmad Aljada ◽  
Paul Davis ◽  
Abdelhadi Rebbaa
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Chorioallantoic Membrane ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Resistance To Doxorubicin

Abstract Thyroid hormone has been recently shown to induce tumor growth and angiogenesis. These angiogenesis modulating activities are initiated at endothelial cell plasma membrane receptor via the integrin αVβ3, at or near the Arg-Gly-Asp (RGD) recognition site on the integrin. In the present study, we have investigated the effect of tetraiodothyroacetic acid (tetrac), a deaminated thyroid hormone analog that inhibits thyroid hormone-binding to the cell surface integrin, on angiogenesis and cancer cell resistance to doxorubicin both in vitro and in vivo. Two angiogenesis models were studied in which vascular endothelial growth factor, VEGF165 or basic fibroblast growth factor, FGF2 (1–2 μg/ml) or thyroid hormone, thyroxin (L-T4 or T3) were used either to induce tube formation in the human dermal micro-vascular endothelial cells (HDMEC), or to stimulate new blood vessel branch formation in the chick chorioallantoic membrane (CAM) models. In both models, Tetrac (0.1–10 μM) inhibited the pro-angiogenesis activity of VEGF, FGF2, L-T4 or T3 by more than 50% at 1.0 uM RT-PCR revealed that tetrac (1–3 μM) decreased abundance of angiopoietin-2 mRNA but did not affect the mRNA levels of angiopoietin-1, in VEGF-exposed endothelial cells, suggesting that specific angiogenic pathways are targeted by this compound. Additionally, microarray was used to examine changes in expression of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) following VEGF treatment with and without tetrac. HDMEC cells treated with VEGF exhibited 3–5-fold increase in MMP-15 and MMP-19 expression and tetrac (3μM), inhibited expression of MMP-15 and MMP-19 by 3–9-fold, respectively. Expression of TIMP-3 was increased 5.4-fold following VEGF and tetrac treatment when compared to treatment with VEGF alone. This finding suggests that part of the mechanism by which tetrac inhibits VEGF-stimulated angiogenesis involves inhibition of certain MMPs and increase in TIMP expression. Investigation of the anti-proliferative function of tetrac was carried out using the αVβ3 expressing breast cancer cells MC7 and their drug resistant counterparts. Interestingly, proliferation of both cell lines was inhibited similarly by tetrac suggesting that this analog may circumvent drug resistance. In fact, tetrac was able to reverse resistance to doxorubicin in vitro and to suppress growth of doxorubicin resistant tumors in nude mice. Inhibition of the drug transporter p-glycoprotein was found to play a key role in mediating the action of tetrac. Taken together, findings presented in this study provide evidence that the anticancer function of tetrac can be attributed to its anti-angiogenic and drug resistance reversal activities.

scholarly journals The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings

2020 ◽  
Vol 31 (11) ◽  
Author(s):  
Christiane Claaßen ◽  
Miriam Dannecker ◽  
Jana Grübel ◽  
Maria-Elli Kotzampasi ◽  
Günter E. M. Tovar ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Chorioallantoic Membrane ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
In Vivo Testing ◽  
Endothelial Growth Factor ◽  
Vegf Release

AbstractBio-based coatings and release systems for pro-angiogenic growth factors are of interest to overcome insufficient vascularization and bio-integration of implants. This study compares different biopolymer-based coatings on polyethylene terephthalate (PET) membranes in terms of coating homogeneity and stability, coating thickness in the swollen state, endothelial cell adhesion, vascular endothelial growth factor (VEGF) release and pro-angiogenic properties. Coatings consisted of carbodiimide cross-linked gelatin type A (GelA), type B (GelB) or albumin (Alb), and heparin (Hep), or they consisted of radically cross-linked gelatin methacryloyl-acetyl (GM5A5) and heparin methacrylate (HepM5). We prepared films with thicknesses of 8–10 µm and found that all coatings were homogeneous after washing. All gelatin-based coatings enhanced the adhesion of primary human endothelial cells compared to the uncoated membrane. The VEGF release was tunable with the loading concentration and dependent on the isoelectric points and hydrophilicities of the biopolymers used for coating: GelA-Hep showed the highest releases, while releases were indistinguishable for GelB-Hep and Alb-Hep, and lowest for GM5A5-HepM5. Interestingly, not only the amount of VEGF released from the coatings determined whether angiogenesis was induced, but a combination of VEGF release, metabolic activity and adhesion of endothelial cells. VEGF releasing GelA-Hep and GelB-Hep coatings induced angiogenesis in a chorioallantoic membrane assay, so that these coatings should be considered for further in vivo testing.

scholarly journals Hyperglycaemia up-regulates placental growth factor (PlGF) expression and secretion in endothelial cells via suppression of PI3 kinase-Akt signalling and activation of FOXO1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samir Sissaoui ◽  
Stuart Egginton ◽  
Ling Ting ◽  
Asif Ahmed ◽  
Peter W. Hewett
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Akt Activation ◽  
Forkhead Box ◽  
Pi3k Activity ◽  
Binding Sequence

AbstractPlacenta growth factor (PlGF) is a pro-inflammatory angiogenic mediator that promotes many pathologies including diabetic complications and atherosclerosis. Widespread endothelial dysfunction precedes the onset of these conditions. As very little is known of the mechanism(s) controlling PlGF expression in pathology we investigated the role of hyperglycaemia in the regulation of PlGF production in endothelial cells. Hyperglycaemia stimulated PlGF secretion in cultured primary endothelial cells, which was suppressed by IGF-1-mediated PI3K/Akt activation. Inhibition of PI3K activity resulted in significant PlGF mRNA up-regulation and protein secretion. Similarly, loss or inhibition of Akt activity significantly increased basal PlGF expression and prevented any further PlGF secretion in hyperglycaemia. Conversely, constitutive Akt activation blocked PlGF secretion irrespective of upstream PI3K activity demonstrating that Akt is a central regulator of PlGF expression. Knock-down of the Forkhead box O-1 (FOXO1) transcription factor, which is negatively regulated by Akt, suppressed both basal and hyperglycaemia-induced PlGF secretion, whilst FOXO1 gain-of-function up-regulated PlGF in vitro and in vivo. FOXO1 association to a FOXO binding sequence identified in the PlGF promoter also increased in hyperglycaemia. This study identifies the PI3K/Akt/FOXO1 signalling axis as a key regulator of PlGF expression and unifying pathway by which PlGF may contribute to common disorders characterised by endothelial dysfunction, providing a target for therapy.

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