Angiogenesis
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Pigment epithelium–derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat retinal pericytes
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Abstract Pigment epithelium–derived factor (PEDF) is a well-known protease inhibitor for angiogenesis in the eye, suggesting that loss
of PEDF in eye is implicated in the pathogenesis of proliferative diabetic retinopathy. Since the role of PEDF in diabetic
retinopathy is unclear, the effect of PEDF on different types of cells constituting the blood vessel has to be checked. Here,
we have investigated the effects of PEDF under hyperglycemic conditions in retinal pericytes, isolated from goat’s eye and
used to analyze the signaling pathway involved. High glucose increased the apoptotic cell death and intr...
Source: Angiogenesis - November 11, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Anti-angiogenic actions of pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor
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In this study, we tested the anti-angiogenic properties
of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, using established in vitro and ex vivo assays in human umbilical
vein endothelial cells (HUVEC) and human metastatic RCC cell lines (ACHN and SN12K1). In vitro, PDTC inhibited proliferation,
capillary tube formation, invasion and trans-differentiation of HUVEC. Ex vivo, PDTC blocked vessel sprouting from aortic
explants and disrupted the integrity of pre-formed vessels. PDTC also inhibited the adhesion of HUVEC and RCC cells to substratum
and inhibited their invasion. PDTC inhibited RCC-induced proliferat...
Source: Angiogenesis - October 30, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Capillary arterialization requires the bone marrow-derived cell (BMC)-specific expression of chemokine (C-C motif) receptor-2, but BMCs do not transdifferentiate into microvascular smooth muscle
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Abstract Chemokine (C-C motif) receptor-2 (CCR2) regulates arteriogenesis and angiogenesis, facilitating the MCP-1-dependent recruitment
of growth factor-secreting bone marrow-derived cells (BMCs). Here, we tested the hypothesis that the BMC-specific expression
of CCR2 is also required for new arteriole formation via capillary arterialization. Following non-ischemic saphenous artery
occlusion, we measured the following in gracilis muscles: monocyte chemotactic protein-1 (MCP-1) in wild-type (WT) C57Bl/6J
mice by ELISA, and capillary arterialization in WT–WT and CCR2−/−–WT (donor–host) bone marrow c...
Source: Angiogenesis - September 24, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
NDRG1 and CRK-I/II are regulators of endothelial cell migration under intermittent hypoxia
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Abstract Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been described to positively influence the tumour
growth by modulating the behaviour of cancer cells as well as of endothelial cells. However, the molecular mechanisms regulated
by IH still remain poorly understood. In this work, the effects of IH were investigated on endothelial cells by a proteomic
approach. Protein abundance variations were studied using fluorescent 2D-Differential in Gel Electrophoresis (2D-DIGE). Amongst
the proteins of which the abundance varied under IH, NDRG1 and CRK-I/II were identified by mass spe...
Source: Angiogenesis - September 17, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Computer-aided quantification of retinal neovascularization
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Abstract Rodent models of retinal angiogenesis play a pivotal role in angiogenesis research. These models are a window to developmental
angiogenesis, to pathological retinopathy, and are also in vivo tools for anti-angiogenic drug screening in cancer and ophthalmic
research. The mouse model of oxygen-induced retinopathy (OIR) has emerged as one of the leading in vivo models for these purposes.
Many of the animal studies that laid the foundation for the recent breakthrough of anti-angiogenic treatments into clinical
practice were performed in the OIR model. However, readouts from the OIR model have ...
Source: Angiogenesis - September 16, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis
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Conclusion Our study, for the first time, shows that targeting of the PI3K pathway using nanoparticles can offer an attractive strategy
for inhibiting tumor angiogenesis.
Content Type Journal ArticleDOI 10.1007/s10456-009-9154-4Authors
Rania Harfouche, Brigham and Women’s Hospital, Harvard Medical School Harvard-MIT Division of Health Sciences and Technology Boston MA 02115 USASudipta Basu, Brigham and Women’s Hospital, Harvard Medical School Harvard-MIT Division of Health Sciences and Technology Boston MA 02115 USAShivani Soni, Brigham and Women’s Hospital, Harvard Medical School Harvard-MIT Div...
Source: Angiogenesis - August 14, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
PEDF inhibits VEGF- and EPO- induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation
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Abstract Retinal angiogenesis in diabetes may lead to visual impairment and even irreversible blindness in people of working age group
worldwide. The main pathological feature of proliferative diabetic retinopathy (PDR) is hypoxia, and overproduction of growth
factors like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). This results in pathological proliferation
of retinal endothelial cells (RECs), leading to new vessel formation (angiogenesis). Inhibition of angiogenesis is a promising
strategy for treatment of PDR and other retinal neovascular disorders. Pigment epithelium-derived facto...
Source: Angiogenesis - August 6, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells
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Abstract Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration
and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have
focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic
potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial
progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen t...
Source: Angiogenesis - June 22, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
A highly selective, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor has potent activity in vitro and in vivo
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Abstract Angiogenesis is a complex process that relies on a variety of growth factors and signaling pathways to stimulate endothelial
cell responses and establish functional blood vessels. Signaling through the vascular endothelial growth factor (VEGF) receptors
is an important mediator of angiogenesis, a hallmark of tumor growth and metastasis. Inhibition of signaling through VEGF
has been clinically validated with FDA-approvals of bevacizumab, sorafenib, and suntinib. Our goal was to discover an orally
available, selective VEGFR-2 inhibitor. A novel oxime, 1-{4-[6-amino-5-(methoxyimino-methyl)-pyrimidin-4-...
Source: Angiogenesis - June 22, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Semaphorins and tumor angiogenesis
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Content Type Journal ArticleCategory ErratumDOI 10.1007/s10456-009-9149-1Authors
Guido Serini, Institute for Cancer Research and Treatment 10060 Torino Candiolo ItalyFederica Maione, Institute for Cancer Research and Treatment 10060 Torino Candiolo ItalyEnrico Giraudo, Institute for Cancer Research and Treatment 10060 Torino Candiolo ItalyFederico Bussolino, Institute for Cancer Research and Treatment 10060 Torino Candiolo Italy
Journal AngiogenesisOnline ISSN 1573-7209Print ISSN 0969-6970 (Source: Angiogenesis)
Source: Angiogenesis - May 27, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Single and combined effects of αvβ3- and α5β1-integrins on capillary tube formation in a human fibrinous matrix
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Abstract The fibrinous exudate of a wound or tumor stroma facilitates angiogenesis. We studied the involvement of RGD-binding integrins
during tube formation in human plasma-derived fibrin clots and human purified fibrin matrices. Capillary-like tube formation
by human microvascular endothelial cells in a 3D plasma-derived fibrinous matrix was induced by FGF-2 and TNF-α and depended
largely on cell-bound u-PA and plasmin activities. While tube formation was minimally affected by the addition of either the
αvβ3-integrin inhibiting mAb LM609 or the α5-integrin inhibiting mAb IIA1, the general RGD-antagonis...
Source: Angiogenesis - May 16, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
The role of the Angiopoietins in vascular morphogenesis
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Abstracts The Angiopoietin/Tie system acts as a vascular specific ligand/receptor system to control endothelial cell survival and vascular
maturation. The Angiopoietin family includes four ligands (Angiopoietin-1, Angiopoietin-2 and Angiopoietin-3/4) and two corresponding
tyrosine kinase receptors (Tie1 and Tie2). Ang-1 and Ang-2 are specific ligands of Tie2 binding the receptor with similar
affinity. Tie2 activation promotes vessel assembly and maturation by mediating survival signals for endothelial cells and
regulating the recruitment of mural cells. Ang-1 acts in a paracrine agonistic manner inducing Tie...
Source: Angiogenesis - May 16, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1
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In conclusion, we provide evidence that Wnt2 acts as an angiogenic factor for non-sinusoidal
endothelium in vitro and in vivo whose target genes undergo complex regulation by the tissue microenvironment.
Content Type Journal ArticleCategory Original paperDOI 10.1007/s10456-009-9145-5Authors
Diana Klein, University Medical Center Mannheim, Ruprecht-Karl University Heidelberg Department of Dermatology, Venereology and Allergology Theodor-Kutzer-Ufer 1-3 68167 Mannheim GermanyAlexandra Demory, University Medical Center Mannheim, Ruprecht-Karl University Heidelberg Department of Dermatology, Venereology and Allergology T...
Source: Angiogenesis - May 15, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Vasculogenesis in infantile hemangioma
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Abstract Infantile hemangioma is a vascular tumor that occurs in 5–10% of infants of European descent. A defining feature of infantile
hemangioma is the dramatic growth and development into a disorganized mass of blood vessels. Subsequently, a slow spontaneous
involution begins around 1 year of age and continues for 4–6 years. The growth and involution of infantile hemangioma is very
different from other vascular tumors and vascular malformations, which do not regress and can occur at any time during childhood
or adult life. Much has been learned from careful study of the tissue morphology and ...
Source: Angiogenesis - May 10, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art
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Abstract It has been more than 20 years since it was first demonstrated that endothelial cells will rapidly form capillary-like structures
in vitro when plated on top of a reconstituted basement membrane extracellular matrix (BME, Matrigel, EHS matrix, etc.). Subsequently,
this morphological differentiation has been demonstrated with a variety of endothelial cells; with endothelial progenitor
cells; and with transformed/immortalized endothelial cells. The differentiation process involves several steps in blood vessel
formation, including cell adhesion, migration, alignment, protease secretion, and tubul...
Source: Angiogenesis - April 28, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Analysis of PPARα-dependent and PPARα-independent transcript regulation following fenofibrate treatment of human endothelial cells
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Abstract Fenofibrate is a synthetic ligand for the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha and has
been widely used in the treatment of metabolic disorders, especially hyperlipemia, due to its lipid-lowering effect. The molecular
mechanism of lipid-lowering is relatively well defined: an activated PPARα forms a PPAR–RXR heterodimer and this regulates
the transcription of genes involved in energy metabolism by binding to PPAR response elements in their promoter regions, so-called
“trans-activation”. In addition, fenofibrate also has anti-inflammatory and anti-athrogenic...
Source: Angiogenesis - April 9, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Shear stress-induced transcriptional regulation via hybrid promoters as a potential tool for promoting angiogenesis
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Abstract Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences
termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous
studies showed that shear stress responsiveness is mediated by a single SSRE, these endogenous promoters often encode for
multiple SSREs. Moreover, hybrid promoters encoding a single SSRE rarely respond to shear stress at the same magnitude as
the endogenous promoter. Thus, to better understand the interplay between the various SSREs, and between SSRE...
Source: Angiogenesis - March 26, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Sendai viral vector mediated angiopoietin-1 gene transfer for experimental ischemic limb disease
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In this study, we constructed a human Ang-1-expressing Sendai viral
vector (SeVhAng-1) and injected it into the ischemic limb of rats. We found that SeVhAng-1 improved the blood flow recovery
and increased the capillary density of the ischemic limb, compared with the controls. We also found that SeVhAng-1 increased
p-Akt during the early period of limb ischemia, and decreased apoptosis in ischemic limb. It suggests that SeVhAng-1 may serve
as a potential therapeutic tool in ischemic limb disease.
Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10456-009-9144-6Authors
Jianhua Huang, Sapporo Medical ...
Source: Angiogenesis - March 26, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Cooperation between integrin ανβ3 and VEGFR2 in angiogenesis
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This article discusses several possible mechanisms reported
by different labs which mediate formation of the complex between VEGFR-2 and αvβ3 on endothelial cells. The pathological consequences and regulatory events involved in this receptor cross-talk are also presented.
Content Type Journal ArticleCategory Review PaperDOI 10.1007/s10456-009-9141-9Authors
Payaningal R. Somanath, The Cleveland Clinic Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, NB50, Lerner Research Institute 9500 Euclid Avenue Cleveland OH 44195 USANikolay L. Malinin, The Cleveland Clinic Joseph ...
Source: Angiogenesis - March 8, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Semaphorins and tumor angiogenesis
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Abstract Semaphorins belong to a large family of proteins well-conserved along evolution from viruses to mammalians. Secreted and membrane-bound
semaphorins participate in a wide range of biological phenomena including development and regeneration of nervous system,
cardiovascular development, and immune system activities. Different classes of semaphorins are bifunctional and often exert
opposite effects (i.e., repellent or attractive) by acting through the plexin receptor family. However, some classes use other
membrane receptors and the same plexin-mediated signals may be modulated by co-receptors, in part...
Source: Angiogenesis - March 6, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro
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We report the effects of inhibiting or inducing CLIC4 expression on distinct aspects of endothelial
cell behavior in vitro. Our experiments utilized RNA interference to establish cultured human endothelial cell lines with
significant reduction of CLIC4 expression, and a CLIC4-expressing lentiviral plasmid was used to establish CLIC4 overexpression
in endothelial cells. We observed no effect on cell migration and a modest effect on cell survival. Reduced CLIC4 expression
decreased cell proliferation, capillary network formation, capillary-like sprouting, and lumen formation. This suggests that
normal endogenous CLIC4 e...
Source: Angiogenesis - February 27, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature
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Abstract Nucleolin is specifically transported to the surface of proliferating endothelial cells in vitro and in vivo. In contrast
to its well defined functions in the nucleus and cytoplasm, the function of cell surface nucleolin is poorly defined. We have
previously identified the nucleolin-binding antibody NCL3 that specifically binds to cell surface nucleolin on angiogenic
blood vessels in vivo and is internalized into the cell. Here, we show that NCL3 inhibits endothelial tube formation in vitro
as well as angiogenesis in the matrigel plaque assay and subcutaneous tumor models in vivo. Intriguingly, the ...
Source: Angiogenesis - February 19, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Role of endothelial progenitors and other bone marrow-derived cells in the development of the tumor vasculature
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Abstract Increasing evidence suggests the importance of bone marrow-derived cells for blood vessel formation (neovascularization) in
tumors, which can occur in two mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from proliferation and sprouting
of existing blood vessels close to the tumor, while vasculogenesis is believed to arise from recruitment of circulating cells,
largely derived from the bone marrow, and de novo clonal formation of blood vessels from these cells. Although bone marrow-derived
cells are crucial for neovascularization, current evidence suggests a promotional role of thes...
Source: Angiogenesis - February 17, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Fibronectins in vascular morphogenesis
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Abstract Fibronectin is an extracellular matrix protein found only in vertebrate organisms containing endothelium-lined vasculature
and is required for cardiovascular development in fish and mice. Fibronectin and its splice variants containing EIIIA and
EIIIB domains are highly upregulated around newly developing vasculature during embryogenesis and in pathological conditions
including atherosclerosis, cardiac hypertrophy, and tumorigenesis. However, their molecular roles in these processes are not
entirely understood. We review genetic studies examining functions of fibronectin and its splice variants durin...
Source: Angiogenesis - February 14, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents
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We report that bleomycin, mitomycin C and
cytoskeletal-disrupting drugs (2-methoxyestradiol, taxol, vincristine, vinblastine, colchicine, nocodazole, and cytochalasin
D) exhibit anti-angiogenic activities of varying potency. Bleomycin and the various cytoskeletal-disrupting drugs inhibited
endothelial cell migration, while mitomycin C had a marginal effect. Both DNA-damaging and cytoskeletal-disrupting drugs decreased
endothelial cell growth in a dose-dependent manner, and this was accompanied by the induction of apoptosis. The growth inhibitory
and apoptotic effects of cytoskeletal-disrupting drugs were the most pron...
Source: Angiogenesis - February 13, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib
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In conclusion, opposite kinetics
of two circulating CD34bright cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused
by sunitinib targeting of immature tumor vessels.
Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10456-009-9133-9Authors
Laura Vroling, VU University Medical Center Department of Medical Oncology CCA 2-54, De Boelelaan 1117 1081 HV Amsterdam The NetherlandsAstrid A. M. van der Veldt, VU University Medical Center Department of Medical Oncology CCA 2-54, De Boelelaan 1117 1081 HV Amsterdam The NetherlandsRichard R. ...
Source: Angiogenesis - February 12, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Molecular differentiation and specialization of vascular beds
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Abstract Transport in the large and complex bodies of vertebrate organisms is mediated by extensive and highly branched tubular networks
that are formed by endothelial cells. Blood vessels are responsible for systemic circulation, while the lymphatic vasculature
drains extravasated plasma, proteins, particles, and cells from the interstitium. Endothelial cells of blood vessels and lymphatic
vessels can be distinguished by the expression of certain molecular markers, which accompany or even contribute to functional
and morphological differences. Even within the blood vessel network, some molecules and pathway...
Source: Angiogenesis - February 12, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling
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Abstract New blood vessels arise initially as blood islands in the process known as vasculogenesis or as new capillary segments produced
through angiogenesis. Angiogenesis itself encompasses two broad processes, namely sprouting (SA) and intussusceptive (IA)
angiogenesis. Primordial capillary plexuses expand through both SA and IA, but subsequent growth and remodeling are achieved
through IA. The latter process proceeds through transluminal tissue pillar formation and subsequent vascular splitting, and
the direction taken by the pillars delineates IA into overt phases, namely: intussusceptive microvascular g...
Source: Angiogenesis - February 5, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Intermittent hypoxia is an angiogenic inducer for endothelial cells: role of HIF-1
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Abstract The presence of hypoxia in tumor and its role in promoting angiogenesis are well-established. Recently, in addition to chronic
hypoxia, cycling or intermittent hypoxia has also been demonstrated. However, its role in inducing new blood vessel formation
is less clear. This work is aimed to investigate whether intermittent hypoxia can induce a pro-angiogenic phenotype in endothelial
cells, in vitro. We studied changes in the expression of genes involved in inflammation and angiogenesis under intermittent
and chronic hypoxia. We evidenced genes specifically expressed under intermittent hypoxia, suggest...
Source: Angiogenesis - January 29, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Endogenous endothelial cell signaling systems maintain vascular stability
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Abstract The function of the endothelium is to provide a network to allow delivery of oxygen and nutrients to tissues throughout the
body. This network comprises adjacent endothelial cells that utilize adherens junction proteins such as vascular endothelial
cadherin (VE-cadherin) to maintain the appropriate level of vascular permeability. The disruption of VE-cadherin interactions
during pathologic settings can lead to excessive vascular leak with adverse effects. Endogenous cell signaling systems have
been defined, which help to maintain the proper level of vascular stability. Perhaps the best described sys...
Source: Angiogenesis - January 27, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Morphological and molecular aspects of physiological vascular morphogenesis
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Abstract The cardiovascular system plays a crucial role in vertebrate development and homeostasis. Several genetic and epigenetic mechanisms
are involved in the early development of the vascular system. During embryonal life, blood vessels first appear as the result
of vasculogenesis, whereas remodeling of the primary vascular plexus occurs by angiogenesis. Many tissue-derived factors are
involved in blood vessel formation and evidence is emerging that endothelial cells themselves represent a source of instructive
signals to non-vascular tissue cells during organ development. This review article summarizes o...
Source: Angiogenesis - January 8, 2009 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells
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Conclusions These results reveal a novel role for HPTPβ in modulating Ang-1-Tie2 signaling and endothelial cell survival.
Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10456-008-9126-0Authors
Orisha K. Yacyshyn, St Michael’s Hospital Terrence Donnelly Heart Centre and Division of Cardiology 30 Bond St. Toronto ON M5B 1W8 CanadaPatrick F. H. Lai, St Michael’s Hospital Terrence Donnelly Heart Centre and Division of Cardiology 30 Bond St. Toronto ON M5B 1W8 CanadaKelly Forse, University of Toronto Human Biology Program Toronto ON M5S 1A8 CanadaKrystyna Teichert-Kuliszewska, St Michae...
Source: Angiogenesis - December 31, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Osteoprotegerin and RANKL differentially regulate angiogenesis and endothelial cell function
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In this study, we assessed the role of OPG and its ligands, receptor activator
of nuclear factor-κB ligand (RANKL) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL), in microvessel formation
using the rat aortic ring model of angiogenesis. OPG was found to promote a twofold increase in angiogenic sprouting in the
aortic ring model, and this effect was inhibited by pre-incubation with a fivefold molar excess of either RANKL or TRAIL.
While TRAIL had no effect upon angiogenesis on its own, RANKL was found to potently inhibit basal and vascular endothelial
growth factor-induced angiogenesis. OPG increa...
Source: Angiogenesis - December 23, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Gα13 regulates MEF2-dependent gene transcription in endothelial cells: role in angiogenesis
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Abstract The α subunit of heterotrimeric G13 protein is required for the embryonic angiogenesis (Offermanns et al., Science 275:533–536,
1997). However, the molecular mechanism of Gα13-dependent angiogenesis is not understood. Here, we show that myocyte-specific
enhancer factor-2 (MEF2) mediates Gα13-dependent angiogenesis. Our data showed that constitutively activated Gα13Q226L stimulated
MEF2-dependent gene transcription. In addition, downregulation of endogenous Gα13 inhibited thrombin-stimulated MEF2-dependent
gene transcription in endothelial cells. Both Ca2+/calmodulin-dependent kinase IV (CaMKI...
Source: Angiogenesis - December 18, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots
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Abstract Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic)
therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis,
which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application
of a novel αvβ3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance
detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-beari...
Source: Angiogenesis - December 10, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function
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Abstract Tie2 is a receptor tyrosine kinase that is expressed predominantly in the endothelium and plays key roles in both physiological
and pathological angiogenesis. The ligands for Tie2, the angiopoietins (Ang), perform opposing functions in vascular maintenance
and angiogenesis; Ang1 regulates vascular quiescence, while Ang2 is thought to promote vascular destabilization and facilitate
angiogenesis. However, the mechanisms responsible for these differences are not understood. To begin to elucidate the molecular
differences between the angiopoietins, we previously developed a specific RNA aptamer inhibito...
Source: Angiogenesis - November 27, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Anti-tumoral effect of active immunotherapy in C57BL/6 mice using a recombinant human VEGF protein as antigen and three chemically unrelated adjuvants
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Abstract Following the clinical success of Bevacizumab, a humanized monoclonal antibody that affects the interaction between vascular
endothelial growth factor (VEGF) and its receptors, blocking tumor-induced angiogenesis has become one of the most important
targets for the development of new cancer therapeutic drugs and procedures. Among the latter, therapeutic vaccination using
VEGF as antigen presents itself as very attractive, with the potential of generating not only a growth factor blocking antibody
response but also a cellular response against tumor cells and stromal elements, which appear to be a maj...
Source: Angiogenesis - November 26, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Angiogenic response to extracorporeal shock wave treatment in murine skin isografts
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Abstract Skin grafts are commonly utilized and proven effective methods of open wound coverage. Revascularization through neoangiogenesis
is a pivotal mechanism for skin graft integration and durability. Extracorporeal shock-wave treatment (ESWT) has been demonstrated
to accelerate wound repair; however, its mechanism-of-action is unclear. We investigated the role of ESWT in early revascularization
of full-thickness skin isografts in a murine model. Cohorts of mice were euthanized and skin grafts were harvested 6 h, 2,
4, and 7 days post grafting ± ESWT. Various aspects of graft neovascu...
Source: Angiogenesis - November 9, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Circulating and imaging markers for angiogenesis
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Abstract Abundant preclinical and indirect clinical data have for several decades convincingly supported the notion that anti-angiogenesis
is an effective strategy for the inhibition of tumor growth. The recent success achieved in patients with metastatic colon
carcinoma using a neutralizing antibody directed against vascular endothelial growth factor (VEGF) has translated preclinical
optimism into a clinical reality.With this transformation in the field of angiogenesis has come a need for reliable surrogate
markers. A surrogate marker by definition serves as a substitute for the underlying process in questi...
Source: Angiogenesis - October 17, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
PPARγ ligands, rosiglitazone and pioglitazone, inhibit bFGF- and VEGF-mediated angiogenesis
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Conclusions These results suggest that PPARγ ligands, pioglitazone and rosiglitazone, in addition to their important regulatory role in
adipogenesis and inflammation, possess anti-angiogenic properties. Thus, PPARγ ligands may be useful in the treatment of diabetic
retinopathy, macular degeneration, and other ocular disorders and may lower the risk to develop cancer in diabetic patients.
Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10456-008-9118-0Authors
Ahmad Aljada, Long Island University, C.W. Post. Department of Biomedical Sciences Brookville NY USALaura O’Connor, The Pharm...
Source: Angiogenesis - September 23, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
A role for planar cell polarity signaling in angiogenesis
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Abstract The planar cell polarity (PCP) pathway is a highly conserved signaling cascade that coordinates both epithelial and axonal
morphogenic movements during development. Angiogenesis also involves the growth and migration of polarized cells, although
the mechanisms underlying their intercellular communication are poorly understood. Here, using cell culture assays, we demonstrate
that inhibition of PCP signaling disrupts endothelial cell growth, polarity, and migration, all of which can be rescued through
downstream activation of this pathway by expression of either Daam-1, Diversin or Inversin. Silencing...
Source: Angiogenesis - September 17, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
The chick embryo chorioallantoic membrane as a model to study tumor metastasis
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Abstract Tumor metastasis represents a major problem in the treatment of patients with different cancers. Specific phenotype and behavior
of metastatic cells derive from specific molecular mechanisms involved in consecutive steps of the metastatic process. Several
in vitro and in vivo experimental models have been utilized, but they cannot completely reproduce and characterize each step
of the metastatic process. This review article is focused on the chick embryo chorioallantoic membrane as an in vivo model
to study the metastatic process.
Content Type Journal ArticleCategory Review PaperDO...
Source: Angiogenesis - September 9, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Farnesyltransferase inhibitors target multiple endothelial cell functions in angiogenesis
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We examined the effects of FTI treatment on a range of assays designed to pick apart the individual functions
of endothelial cells during angiogenesis. We found that FTIs inhibit endothelial cell proliferation, causing a failure of
mitosis and accumulation of binucleate cells. FTIs also block the directional migration of endothelial cells toward VEGF,
the major pro-angiogenic factor in adult tissues. In a co-culture assay of angiogenesis, FTI treatment significantly inhibits
tube formation, but has no effect on pre-existing structures. Defects in tube formation could be replicated by specific targeting
of endothelial ...
Source: Angiogenesis - August 30, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
The discovery of the placental growth factor and its role in angiogenesis: a historical review
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Abstract The placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family,
which was discovered in 1991 by an Italian scientist, Maria Graziella Persico. Dr Persico cloned and purified PlGF and determined
its structure by crystallography resolution. Furthermore, she identified VEGF receptor-1 (VEGFR-1) as the receptor for PlGF,
and in collaboration with Dr Peter Carmeliet in Leuven, she generated evidence that loss of PlGF does not affect development,
reproduction, or postnatal life. PlGF is expressed primarily in the placenta and is up-regulated i...
Source: Angiogenesis - June 21, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Lysophosphatidic acid (LPA) and angiogenesis
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Abstract Lysophosphatidic acid (LPA) is a simple lipid with many important biological functions such as the regulation of cellular
proliferation, cellular migration, differentiation, and suppression of apoptosis. Although a direct angiogenic effect of LPA
has not been reported to date, there are indications that LPA promotes angiogenesis. In addition, LPA is a chemoattractant
for cultured endothelial cells and promotes barrier function in such cultures [1]. To test the hypothesis that LPA is angiogenic, we used the chicken chorio-allantoic membrane (CAM) assay. Sequence analysis
of the cloned, full-length ch...
Source: Angiogenesis - May 27, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Angiogenic-regulatory network revealed by molecular profiling heart tissue following Akt1 induction in endothelial cells
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Abstract Akt is a pivotal signaling molecule involved in the regulation of angiogenesis. In order to further elucidate the role of
Akt1 in blood vessel development, a tetracycline-regulated transgenic system was utilized to conditionally activate Akt1 signaling
in endothelial cells to examine transcript expression changes associated with angiogenesis in the heart. Induction of Akt1
over the course of 6 weeks led to a 33% increase in capillary density without affecting overall heart growth. Transcript expression
profiles in the hearts were analyzed with an Affymetrix GeneChip Mouse Expression Set 430 2.0...
Source: Angiogenesis - May 20, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing
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Abstract Previous in vivo and in vitro studies have shown that Akt1 serves as a crucial regulator of vascular maturation, extracellular
matrix composition, and angiogenesis in tumors. Hence, we hypothesized that Akt1 may be necessary for other angiogenesis-dependent
processes, including wound healing. Using Akt1
−/− and Akt2
−/− mice, we demonstrate that deficiency of Akt1, but not Akt2, results in impaired assembly of collagen in skin wounds and around
the blood vessels. Wounds in Akt1
−/− mice, but not in Akt2
−/− mice, were characterized by reduced vascular area as well as imp...
Source: Angiogenesis - April 16, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Novel function of the thyroid hormone analog tetraiodothyroacetic acid: a cancer chemosensitizing and anti-cancer agent
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Abstract Previous studies from our laboratory have demonstrated that thyroid hormones play a key role in cancer progression. In addition,
a deaminated form, tetraiodothyroacetic acid (tetrac), that antagonizes the proliferative action of these hormones was found
to possess anti-cancer functions through its ability to inhibit cellular proliferation and angiogenesis. The present study
was undertaken to investigate whether tetrac could also suppress the development of drug resistance, known as a causative
factor of disease relapse. Tetrac was shown to enhance cellular response in vitro to doxorubicin, etoposide...
Source: Angiogenesis - April 3, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
VEGF165 expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing’s sarcoma vasculature
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Abstract We previously demonstrated that bone marrow (BM) cells migrate to Ewing’s tumors and differentiate into endothelial cells
within the tumor vasculature. Recent evidence suggests that the roles of BM cells in tumors are more diverse. We investigated
whether non-endothelial cell types critical for tumor vessel development are also derived from migrated BM cells. We utilized
BM transplantation with GFP+ transgenic mice as BM donors and nude mice as recipients to track the fate of migrated BM cells. After engraftment, we injected
recipient mice either subcutaneously or intramuscularly with Ewing’s sa...
Source: Angiogenesis - March 16, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
Anti-angiogenic activity of sesterterpenes; natural product inhibitors of FGF-2-induced angiogenesis
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Abstract Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is of physiological and pathological importance.
We have investigated the anti-angiogenic potential of two naturally occurring sesterterpenes, leucosesterterpenone (compound
1) and leucosterlactone (compound 2) isolated from the Himalayan plant Leucosceptrum canum and identified as having biological activity in preliminary screening. Compound 1 inhibited fibroblast growth factor-2-induced proliferation, migration in a wounding assay, chemotaxis and tube formation
with small vessel (human dermal) and large vessel (bovine a...
Source: Angiogenesis - March 11, 2008 Category: Molecular Biology Tags: Angiogenesis Source Type: journals
