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Angiogenesis

About: Angiogenesis is a research topic. Over the lifetime, 58248 publications have been published within this topic receiving 3290129 citations. The topic is also known as: blood vessel formation from pre-existing blood vessels & GO:0001525.


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Journal ArticleDOI
TL;DR: In this article, the development of blood vessels from in situ differentiating endothelial cells of blood islands, a process which is called vasculogenesis, was induced by injecting ESC into the peritoneal cavity of syngeneic mice.
Abstract: Embryonic stem cells (ESC) have been established previously from the inner cell mass cells of mouse blastocysts. In suspension culture, they spontaneously differentiate to blood-island-containing cystic embryoid bodies (CEB). The development of blood vessels from in situ differentiating endothelial cells of blood islands, a process which we call vasculogenesis, was induced by injecting ESC into the peritoneal cavity of syngeneic mice. In the peritoneum, fusion of blood islands and formation of an in vivo-like primary capillary plexus occurred. Transplantation of ESC and ESC-derived complex and cystic embryoid bodies (ESC-CEB) onto the quail chorioallantoic membrane (CAM) induced an angiogenic response, which was directed by nonyolk sac endoderm structures. Neither yolk sac endoderm from ESC-CEB nor normal mouse yolk sac tissue induced angiogenesis on the quail CAM. Extracts from ESC-CEB stimulated the proliferation of capillary endothelial cells in vitro. Mitogenic activity increase during in vitro culture and differentiation of ESC. Almost all growth factor activity was associated with the cells. The ESC-CEB derived endothelial cell growth factor bound to heparin-sepharose. The identification of acidic fibroblast growth factor (FGF)in heparin-sepharose-purified material was accomplished by immunoblot experiments involving antibodies against acidic and basic FGF. We conclude that vasculogenesis, the development of blood vessels from in situ differentiating endothelial cells, and angiogenesis, the sprouting of capillaries from preexisting vessels are very early events during embryogenesis which can be studied using ESC differentiating in vitro. Our results suggest that vasculogenesis and angiogenesis are differently regulated.

678 citations

Journal ArticleDOI
23 Sep 1983-Science
TL;DR: The control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.
Abstract: When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.

678 citations

Journal ArticleDOI
07 Apr 2005-Nature
TL;DR: A fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration, is supported.
Abstract: Aquaporin-1 (AQP1) is a water channel protein expressed widely in vascular endothelia, where it increases cell membrane water permeability. The role of AQP1 in endothelial cell function is unknown. Here we show remarkably impaired tumour growth in AQP1-null mice after subcutaneous or intracranial tumour cell implantation, with reduced tumour vascularity and extensive necrosis. A new mechanism for the impaired angiogenesis was established from cell culture studies. Although adhesion and proliferation were similar in primary cultures of aortic endothelia from wild-type and from AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells, with abnormal vessel formation in vitro. Stable transfection of non-endothelial cells with AQP1 or with a structurally different water-selective transporter (AQP4) accelerated cell migration and wound healing in vitro. Motile AQP1-expressing cells had prominent membrane ruffles at the leading edge with polarization of AQP1 protein to lamellipodia, where rapid water fluxes occur. Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration.

678 citations

Journal Article
TL;DR: In this article, the authors used oligonucleotide-based DNA microarrays to analyze transcriptional changes resulting from constitutive Ras signaling and found that Ras signaling leads to a significant induction of Interleukin-8 (IL-8) mRNA, which is accompanied by a corresponding increase in protein levels.
Abstract: 1749 Ras proteins are important regulators of cell proliferation and their constitutive activation is a key event in cancer development. To discover novel effector pathways that might contribute to the oncogenic properties of Ras, we used oligonucleotide-based DNA microarrays to analyze transcriptional changes resulting from constitutive Ras signaling. We performed the expression analyses with HeLa stable cell lines expressing activated RasG12→V transgenes under a tetracycline responsive promoter (Tet-Off™ Expression System). This system not only mediates tight on/off regulation of gene expression; it also permits the titration of protein levels on a single cell basis allowing the study of dose dependent aspects of gene activity. Ras signaling leads to a significant induction of Interleukin-8 (IL-8) mRNA, which is accompanied by a corresponding increase in protein levels. IL-8 is a chemotactic factor for leukocytes and closely associated with the initiation of an acute inflammatory response. Analysis of signal transduction pathways that link Ras to IL-8 up-regulation suggests a direct effect of Ras on the IL-8 promoter, mediated by the synergistic activation of both MAPK-cascades and the PI3K > NFκB pathway. In addition, the Ras-induced accumulation of IL-8 protein is dependent on the activation of p38 MAP-kinase through a post-transcriptional mechanism involving an increase in IL-8 mRNA stability. Investigation of the functional importance of IL-8 in the context of tumorigenesis shows that IL-8 plays a decisive role in RasV12-mediated acceleration of tumor growth in a nude mouse xenograft model. Ablation of IL-8 function is accompanied by a significant reduction in tumor size. This effect is not due to decreased cell proliferation rates, since we observe no change in the mitogenic index of tumors after inhibition of IL-8. However, tumors devoid of functional IL-8 show a marked reduction in vascularization accompanied by vast tissue necrosis. These observations can be correlated with an IL-8-mediated initiation of an early inflammatory reaction in developing neoplasms that triggers tumor vascularization. In addition, IL-8 may act directly to support angiogenesis by promoting endothelial cell proliferation and migration. These results provide a novel mechanism by which tumor cells harboring oncogenic Ras can appropriate inflammatory mediators to recruit immune cells to the tumor site and facilitate neo-angiogenesis, thus setting the stage for subsequent progression to malignancy.

675 citations

Journal ArticleDOI
TL;DR: Angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.
Abstract: Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.

675 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
20234,761
20225,433
20212,598
20202,542
20192,517