Document Detail

Age-related impairment of endothelial progenitor cell migration correlates with structural alterations of heparan sulfate proteoglycans.
MedLine Citation:
PMID:  23190312     Owner:  NLM     Status:  MEDLINE    
Aging poses one of the largest risk factors for the development of cardiovascular disease. The increased propensity toward vascular pathology with advancing age maybe explained, in part, by a reduction in the ability of circulating endothelial progenitor cells to contribute to vascular repair and regeneration. Although there is evidence to suggest that colony forming unit-Hill cells and circulating angiogenic cells are subject to age-associated changes that impair their function, the impact of aging on human outgrowth endothelial cell (OEC) function has been less studied. We demonstrate that OECs isolated from cord blood or peripheral blood samples from young and old individuals exhibit different characteristics in terms of their migratory capacity. In addition, age-related structural changes were discovered in OEC heparan sulfate (HS), a glycocalyx component that is essential in many signalling pathways. An age-associated decline in the migratory response of OECs toward a gradient of VEGF significantly correlated with a reduction in the relative percentage of the trisulfated disaccharide, 2-O-sulfated-uronic acid, N, 6-O-sulfated-glucosamine (UA[2S]-GlcNS[6S]), within OEC cell surface HS polysaccharide chains. Furthermore, disruption of cell surface HS reduced the migratory response of peripheral blood-derived OECs isolated from young subjects to levels similar to that observed for OECs from older individuals. Together these findings suggest that aging is associated with alterations in the fine structure of HS on the cell surface of OECs. Such changes may modulate the migration, homing, and engraftment capacity of these repair cells, thereby contributing to the progression of endothelial dysfunction and age-related vascular pathologies.
Kate A Williamson; Andrew Hamilton; John A Reynolds; Peter Sipos; Ian Crocker; Sally E Stringer; Yvonne M Alexander
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Aging cell     Volume:  12     ISSN:  1474-9726     ISO Abbreviation:  Aging Cell     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-09-30     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101130839     Medline TA:  Aging Cell     Country:  England    
Other Details:
Languages:  eng     Pagination:  139-47     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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MeSH Terms
Age Factors
Apoptosis / physiology
Blood Cells / cytology
Cell Growth Processes / physiology
Cell Movement / physiology*
Cell Survival / physiology
Endothelial Cells / cytology*,  metabolism*
Fetal Blood / cytology
Heparan Sulfate Proteoglycans / metabolism*
Stem Cells / cytology*,  metabolism*
Grant Support
G1000417//Medical Research Council; //Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Heparan Sulfate Proteoglycans

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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