scholarly journals Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

2003 ◽  
Vol 9 (3) ◽  
pp. 239-248 ◽  
Author(s):  
N. Kubis ◽  
B.I. Levy
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Endothelial Cell Migration ◽  
Angiogenic Growth Factors ◽  
Blood Vessel Formation ◽  
Vasculogenesis And Angiogenesis ◽  
Cell Migration And Proliferation ◽  
Extracellular Proteolysis ◽  
Coagulation And Fibrinolysis

Angiogenesis, defined as a new blood vessel formation from a pre-existing vessel, is initiated by angiogenic growth factors and their receptors that induce endothelial cell migration and proliferation. Extracellular proteolysis is essential for deassembly and reassembly of endothelial cells to their environmental matrix. The aim of this review is to update data on the role of the coagulation and fibrinolysis system, metalloproteinases and adhesion molecules during this step of angiogenesis.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

Urokinase Receptor (uPAR)-Dependent Integrin Redistribution Represents a Central Mechanism for Growth Factor Induced Endothelial Cell Migration

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2119-2119 ◽  
Author(s):  
Rene Novotny ◽  
Matthias Unseld ◽  
Marina Poettler ◽  
Christoph Zielinski ◽  
Bernd Binder ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Binding Site ◽  
Protein Interaction ◽  
Conflicts Of Interest ◽  
Endothelial Cell Migration ◽  
Angiogenic Growth Factors

Abstract Abstract 2119 Tumor angiogenesis is induced when the net balance of pro- and antiangiogenic molecules is tipped in favor of angiogenesis, the so called ‘angiogenic switch’. Recently, we described a mechanism how VEGF induces pro-urokinase (pro-uPA) activation, which led to uPAR-complex formation and internalization of beta-1 integrins into the endosomal compartment via LDLR-proteins such as ApoER2 or VLDLR. Thereby, uPAR plays a central role for VEGF-induced endothelial cell migration. Here, we describe that uPAR-induced integrin internalization and redistribution to the leading edge is not only limited to VEGF-induced endothelial cell migration, but plays a central role for others angiogenic growth factors such as fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF) as well as epidermal growth factor (EGF). Furthermore, we found that a hitherto undescribed binding site on domain 3 of uPAR for direct LDLR-protein interaction is required and sufficient for uPAR-dependent integrin redistribution. Interference with the uPAR/integrin internalization either by the Receptor Associated Protein (RAP) or a specific LDLR-binding site mimicking peptide (P1), the migratory response of endothelial cells towards the growth factors VEGF, HGF, FGF-2, or EGF was almost blocked (20.24% ± 4.56%). Consistently, expression of a mutated uPAR lacking interaction site for LDLR-proteins in uPAR-/- endothelial cells via a retroviral construct led to reduced invasive response towards angiogenic growth factors in vitro as well as in a Matrigel plug in vivo assay. From these data we conclude that uPAR/LDLR-protein interaction represents a central molecule in growth factor-induced endothelial cell behavior, which might open a new avenue for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.

Role of Growth Factors and Endothelial Cells in Therapeutic Angiogenesis and Tissue Engineering

2006 ◽  
Vol 1 (3) ◽  
pp. 333-343 ◽  
Author(s):  
Masashi Nomi ◽  
Hideaki Miyake ◽  
Yoshifumi Sugita ◽  
Masato Fujisawa ◽  
Shay Soker
Keyword(s):  
Tissue Engineering ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Therapeutic Angiogenesis

scholarly journals The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Francesco Drago ◽  
Giulia Ciccarese ◽  
Francesco Broccolo ◽  
Massimo Ghio ◽  
Paola Contini ◽  
...  
Keyword(s):  
Growth Factors ◽  
Human Herpesvirus ◽  
Inflammatory Cells ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Pityriasis Rosea ◽  
Vasculogenesis And Angiogenesis ◽  
Endothelial Growth Factor

Introduction. Pityriasis rosea (PR) is an exanthematous disease related to human herpesvirus- (HHV-) 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied.Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis.Materials and Methods. Interleukin- (IL-) 1, IL-6, IL-17, interferon- (IFN-)γ, tumor necrosis factor- (TNF-)α, vascular endothelial growth factor (VEGF), granulocyte colony stimulating factor (G-CSF), and chemokines, CXCL8 (IL-8) and CXCL10 (IP-10), were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days).Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γhas a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis.Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

Role of angiogenic growth factors in transplant coronary artery disease

2004 ◽  
Vol 36 (3) ◽  
pp. 184-193 ◽  
Author(s):  
Karl Lemström ◽  
Antti Nykänen ◽  
Jussi Tikkanen ◽  
Rainer Krebs ◽  
Roope Sihvola ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Growth Factors ◽  
Coronary Artery ◽  
Angiogenic Growth Factors ◽  
Artery Disease

scholarly journals Immunology and Genetic of Preeclampsia

2006 ◽  
Vol 13 (2-4) ◽  
pp. 197-201 ◽  
Author(s):  
Norma C. Serrano
Keyword(s):  
Developing Countries ◽  
Growth Factors ◽  
Fetal Death ◽  
Preventive Strategies ◽  
Angiogenic Growth Factors ◽  
Third Trimester ◽  
Maternal Circulation ◽  
Familial Predisposition ◽  
The Third

Preeclampsia is a disease characterized by hypertension and proteinuria in the third trimester of pregnancy. Preeclampsia is a major cause of maternal mortality, and fetal death, especially in developing countries, but its aetiology remains unclear. Key findings support a causal role of superficial placentation driven by immune mal maladaptation, which then lead to reduced concentrations of angiogenic growth factors and to an increase in placental debris in the maternal circulation resulting in a maternal inflammatory response. Epidemiological research has consistently demonstrated a substantial familial predisposition to preeclampsia. Unfortunately, the conquest of the genes explaining such a individual susceptibility has been proved to be a hard task. However, genetics will also inform us about causality of environmental factors, and then serve as a tool to prioritize therapeutic targets for preventive strategies.

Expression of Soluble Syndecan-1 or Heparanase by Myeloma Cells Enhances Levels of Angiogenic Growth Factors Present in Endothelial Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3448-3448
Author(s):  
Yang Yang ◽  
Ashley Elizabeth Frith ◽  
Allison Theus ◽  
Veronica Macleod ◽  
Ralph D. Sanderson
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Fold Increase ◽  
Conditioned Media ◽  
High Rate ◽  
In Vivo Studies ◽  
Angiogenic Growth Factors ◽  
Myeloma Cells

Abstract Multiple myeloma is a devastating cancer with a high rate of morbidity and mortality. Our previous in vivo studies demonstrate that both shed syndecan-1 and heparanase can promote myeloma tumor growth, metastasis and angiogenesis. To examine the mechanism underlying this enhanced angiogenesis, human umbilical vein endothelial cells (HUVEC) were cocultured with cells of the CAG myeloma cell line (vector-only controls, CAGcontrol) or CAG cells engineered to express high levels of either soluble syndecan-1 ectodomain (CAGssyn1 ) or heparanase ( CAGHPSE ). After coculture for 48 hours, levels of angiogenic growth factors present in the endothelial cells were examined. The goal was to determine if expression of either soluble syndecan-1 or heparanase by CAG myeloma cells altered growth factor levels relative to those present when control CAG cells were used. Co-culture with CAGssyn1 or CAGHPSE cells did not enhance endothelial levels of FGF-2, while levels of hepatoma-derived growth factor (HDGF) and hepatocyte growth factor (HGF) were elevated in endothelia growing in the presence of CAGssyn1 cells but not CAGHPSE cells or CAGcontrol cells. However, VEGF levels present in endothelial cells were substantially enhanced by the presence of CAGssyn1 (1.9-fold increase) or CAGHPSE cells (1.6-fold increase). Surprisingly, levels of VEGF in conditioned media of cocultures containing either CAGssyn1 or CAGHPSE cells was low. In contrast, when cultured in the absence of HUVECs, VEGF levels were elevated in conditioned media of both CAGssyn1and CAGHPSE cells. Addition of this conditioned media containing high levels of VEGF to HUVECs growing in the absence of CAG cells did not result in an elevation of VEGF levels in the endothelial cells. Together, these experiments suggest that VEGF expression is upregulated in CAG cells expressing high levels of shed syndecan-1 or heparanase and that VEGF becomes associated with the endothelial cells only when they are cultured in the presence of the myeloma cells. This cross-talk between myeloma and endothelial cells may lead to the enhanced angiogenesis that occurs in vivo in tumors formed by myeloma cells producing high levels of shed syndecan-1 and/or heparanase.

Co-Culture of Myeloma and Endothelial Cells: Defibrotide Downregulates Heparanase and Pro-Angiogenic Growth Factors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2513-2513 ◽  
Author(s):  
Cinara Echart ◽  
Maria Distaso ◽  
Laura Ferro ◽  
Mario Boccadoro ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Conditioned Media ◽  
Angiogenic Growth Factors ◽  
Factor Expression ◽  
Key Factor ◽  
Growth Factor Expression ◽  
Rpmi 8226

Abstract Introduction: Heparanase (HPSE) expression in humans has been associated with advanced progression and metastasis of many tumor types, including multiple myeloma (MM), where its activity is correlated with altered gene expression that may promote an aggressive tumor phenotype with high microvessel density (ref). These findings indicate an important role of HPSE in regulating metastasis, angiogenesis and progression of MM. Defibrotide (DF) is an orally bio-available polydisperse oligonucleotide with anti-thrombotic, pro-fibrinolytic, anti-adhesive and anti-angiogenic properties. Recently, we have shown that DF is able to downregulate HPSE gene expression and activity in MM cell lines (International myeloma workshop, Greece, 2007). Methods: We investigated whether the expression of HPSE and angiogenic growth factors (FGF-2 and VEGF) in human microvascular endothelial cells (HMEC) are modified by co-culture with MM cells or by growing in the media of MM cells. In addition, we evaluated whether DF has activity in regulating the expression of HPSE, FGF-2 and VEGF in HMEC co-cultured with MM cells. We then tested the effect of DF on the invasiveness of MM cells activated with HPSE. HMEC cells were co-cultured with RPMI 8226 MM cells for 48h in the presence and absence of DF (at dose of 150μg/ml). HMEC was also grown alone for 48h in MM cell-conditioned media. The expression of HPSE and angiogenic growth factors (FGF-2 and VEGF) present in endothelial cells were examined through real time polymerase chain reaction (RT-PCR) of cDNA prepared from HMEC. Tumor invasion was evaluated using the BD BioCoat MatrigelTM invasion system (BD Bioscience). Results: Coculture with RPMI 8226 cells substantially induced the expression of HPSE (7.2 fold) and angiogenic growth factors (3-5 fold) in HMEC compared with endothelial cells growing alone. DF was able to downregulate HPSE, FGF-2 and VEGF gene expression in HMEC co-cultured with RPMI 8226 cells (4.0; 6.0-8.0 fold, respectively). Surprisingly, addition of conditioned media in absence of MM cells resulted in 6.5 fold of elevation of HPSE but not growth factors expression in HMEC. These results show that components released by MM cells are sufficient to modulate HPSE. However, to alter growth factor expression, HMEC needed to be culture in the presence of RPMI 8226 cells. Additionally, HPSE increased the invasiveness of RPMI 8226 cells and DF was able to significantly decrease MM invasiveness in the Matrigel assay by 50% (p<0.05). Conclusion: Taken together, these results suggest that cross-talk between MM and endothelial cells leads to enhanced angiogenesis. HPSE is a key factor in this process, correlating with both angiogenic stimulus and MM progression. Moreover, DF is able to downregulate HSPE and growth factor expression in activated HMEC induced by MM, as well as reducing the invasiveness of MM in this system. These observations suggest a potent potential anti-tumor effect of DF and support further preclinical evaluation in MM models as well as ongoing clinical studies in this setting.

Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2304-2311
Author(s):  
Daotai Nie ◽  
Keqin Tang ◽  
Clement Diglio ◽  
Kenneth V. Honn
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Critical Role ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
12 Lipoxygenase

Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a multistep, highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, tube differentiation, and survival. Eicosanoids, arachidonic acid (AA)-derived metabolites, have potent biologic activities on vascular endothelial cells. Endothelial cells can synthesize various eicosanoids, including the 12-lipoxygenase (LOX) product 12(S)-hydroxyeicosatetraenoic acid (HETE). Here we demonstrate that endogenous 12-LOX is involved in endothelial cell angiogenic responses. First, the 12-LOX inhibitor, N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP), reduced endothelial cell proliferation stimulated either by basic fibroblast growth factor (bFGF) or by vascular endothelial growth factor (VEGF). Second, 12-LOX inhibitors blocked VEGF-induced endothelial cell migration, and this blockage could be partially reversed by the addition of 12(S)-HETE. Third, pretreatment of an angiogenic endothelial cell line, RV-ECT, with BHPP significantly inhibited the formation of tubelike/cordlike structures within Matrigel. Fourth, overexpression of 12-LOX in the CD4 endothelial cell line significantly stimulated cell migration and tube differentiation. In agreement with the critical role of 12-LOX in endothelial cell angiogenic responses in vitro, the 12-LOX inhibitor BHPP significantly reduced bFGF-induced angiogenesis in vivo using a Matrigel implantation bioassay. These findings demonstrate that AA metabolism in endothelial cells, especially the 12-LOX pathway, plays a critical role in angiogenesis.

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