| Angiogenesis and vascular remodelling in normal and cancerous tissues. | |
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MedLine Citation:
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PMID: 18941752 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vascular development and homeostasis are underpinned by two fundamental features: the generation of new vessels to meet the metabolic demands of under-perfused regions and the elimination of vessels that do not sustain flow. In this paper we develop the first multiscale model of vascular tissue growth that combines blood flow, angiogenesis, vascular remodelling and the subcellular and tissue scale dynamics of multiple cell populations. Simulations show that vessel pruning, due to low wall shear stress, is highly sensitive to the pressure drop across a vascular network, the degree of pruning increasing as the pressure drop increases. In the model, low tissue oxygen levels alter the internal dynamics of normal cells, causing them to release vascular endothelial growth factor (VEGF), which stimulates angiogenic sprouting. Consequently, the level of blood oxygenation regulates the extent of angiogenesis, with higher oxygenation leading to fewer vessels. Simulations show that network remodelling (and de novo network formation) is best achieved via an appropriate balance between pruning and angiogenesis. An important factor is the strength of endothelial tip cell chemotaxis in response to VEGF. When a cluster of tumour cells is introduced into normal tissue, as the tumour grows hypoxic regions form, producing high levels of VEGF that stimulate angiogenesis and cause the vascular density to exceed that for normal tissue. If the original vessel network is sufficiently sparse then the tumour may remain localised near its parent vessel until new vessels bridge the gap to an adjacent vessel. This can lead to metastable periods, during which the tumour burden is approximately constant, followed by periods of rapid growth. |
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Authors:
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Markus R Owen; Tomás Alarcón; Philip K Maini; Helen M Byrne |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-22 |
Journal Detail:
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Title: Journal of mathematical biology Volume: 58 ISSN: 0303-6812 ISO Abbreviation: J Math Biol Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-01-14 Completed Date: 2009-03-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502105 Medline TA: J Math Biol Country: Germany |
Other Details:
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Languages: eng Pagination: 689-721 Citation Subset: IM |
Affiliation:
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School of Mathematical Sciences, University of Nottingham, Nottingham, UK. markus.owen@nottingham.ac.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Hemodynamics Humans Mathematical Concepts Models, Biological* Neoplasms / blood supply*, physiopathology Neovascularization, Pathologic* Neovascularization, Physiologic* Vascular Endothelial Growth Factor A / physiology |
| Grant Support | |
ID/Acronym/Agency:
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U56CA113004/CA/NCI NIH HHS; //Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Vascular Endothelial Growth Factor A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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