Document Detail


Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice.
MedLine Citation:
PMID:  21765212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Eleni Bazigou; Oliver T A Lyons; Alberto Smith; Graham E Venn; Celia Cope; Nigel A Brown; Taija Makinen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-18
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-01     Completed Date:  2011-10-03     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2984-92     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
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:
G1000327//Medical Research Council; //British Heart Foundation; //Cancer Research UK; //Medical Research Council
Chemical
Reg. No./Substance:
0/Ephrin-B2; 0/Fibronectins; 0/Integrin alpha Chains; 0/integrin alpha9
Comments/Corrections

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