Document Detail


Glycocalyx modulates the motility and proliferative response of vascular endothelium to fluid shear stress.
MedLine Citation:
PMID:  17468337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Flow-induced mechanotransduction in vascular endothelial cells has been studied over the years with a major focus on putative connections between disturbed flow and atherosclerosis. Recent studies have brought in a new perspective that the glycocalyx, a structure decorating the luminal surface of vascular endothelium, may play an important role in the mechanotransduction. This study reports that modifying the amount of the glycocalyx affects both short-term and long-term shear responses significantly. It is well established that after 24 h of laminar flow, endothelial cells align in the direction of flow and their proliferation is suppressed. We report here that by removing the glycocalyx by using the specific enzyme heparinase III, endothelial cells no longer align under flow after 24 h and they proliferate as if there were no flow present. In addition, confluent endothelial cells respond rapidly to flow by decreasing their migration speed by 40% and increasing the amount of vascular endothelial cadherin in the cell-cell junctions. These responses are not observed in the cells treated with heparinase III. Heparan sulfate proteoglycans (a major component of the glycocalyx) redistribute after 24 h of flow application from a uniform surface profile to a distinct peripheral pattern with most molecules detected above cell-cell junctions. We conclude that the presence of the glycocalyx is necessary for the endothelial cells to respond to fluid shear, and the glycocalyx itself is modulated by the flow. The redistribution of the glycocalyx also appears to serve as a cell-adaptive mechanism by reducing the shear gradients that the cell surface experiences.
Authors:
Yu Yao; Aleksandr Rabodzey; C Forbes Dewey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-04-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-03     Completed Date:  2007-09-18     Revised Date:  2008-02-22    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1023-30     Citation Subset:  IM    
Affiliation:
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139-4307, USA. yuyao@mit.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / metabolism
Cadherins / metabolism
Cattle
Cell Movement*
Cell Proliferation*
Cells, Cultured
Endothelial Cells / metabolism*
Endothelium, Vascular / cytology,  metabolism*
Glycocalyx / metabolism*
Hemorheology / methods
Heparan Sulfate Proteoglycans / metabolism
Humans
Intercellular Junctions / metabolism
Mechanotransduction, Cellular*
Polysaccharide-Lyases / metabolism
Protein Transport
Stress, Mechanical
Time Factors
Grant Support
ID/Acronym/Agency:
1 P01 HL64858-01A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Cadherins; 0/Heparan Sulfate Proteoglycans; 0/cadherin 5; EC 4.2.2.-/Polysaccharide-Lyases; EC 4.2.2.8/heparitinsulfate lyase

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