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Pigment epithelium–derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat retinal pericytesemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 inhibitoremail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 muscleemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 hypoxiaemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 neovascularizationemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 phosphorylationemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 vivoemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 matrixemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 morphogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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-1email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 hemangiomaemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 artemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 diseaseemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 vitroemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 vasculatureemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 vasculatureemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 morphogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 agentsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 sunitinibemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 bedsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 remodelingemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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-1email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 stabilityemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 morphogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 functionemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 dotsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 functionemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 adjuvantsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 isograftsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 metastasisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 reviewemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 healingemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 agentemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 vasculatureemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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 angiogenesisemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
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