Document Detail

Absence of venous valves in mice lacking Connexin37.
MedLine Citation:
PMID:  23142761     Owner:  NLM     Status:  MEDLINE    
Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell-cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.
Stephanie J Munger; John D Kanady; Alexander M Simon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  Developmental biology     Volume:  373     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-02-21     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  338-48     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Connexin 43 / metabolism
Connexins / deficiency*,  metabolism
Endothelium / metabolism
Extremities / surgery
Mice, Inbred C57BL
Protein Transport
Regional Blood Flow
Saphenous Vein / metabolism,  pathology
Skin / blood supply
Venous Valves / abnormalities*,  metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/Connexin 43; 0/Connexins; 0/connexin 37; 0/connexin 47

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