| Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. | |
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MedLine Citation:
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PMID: 21765212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity. |
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Authors:
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Eleni Bazigou; Oliver T A Lyons; Alberto Smith; Graham E Venn; Celia Cope; Nigel A Brown; Taija Makinen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-07-18 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 121 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-01 Completed Date: 2011-10-03 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 2984-92 Citation Subset: AIM; IM |
Affiliation:
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Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Endothelial Cells / cytology Endothelium, Vascular / physiology Ephrin-B2 / metabolism Fibronectins / metabolism Humans Hypertension / genetics Integrin alpha Chains / metabolism Lymphangiogenesis / genetics*, physiology* Mice Mice, Transgenic Models, Biological Phenotype Transgenes Venous Valves / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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//British Heart Foundation; //Cancer Research UK; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Ephrin-B2; 0/Fibronectins; 0/Integrin alpha Chains; 0/integrin alpha9 |
| Comments/Corrections | |
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