Article

N-cadherin upregulation and function in response of smooth muscle cells to arterial injury.

Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Arteriosclerosis Thrombosis and Vascular Biology (impact factor: 6.37). 01/2003; 22(12):1972-7. pp.1972-7
Source: PubMed

ABSTRACT Smooth muscle cell migration is critical to neointimal formation after arterial injury. The purpose of this study was to elucidate the regulation and functional significance of cell-cell adhesion via adherens junctions during this process.
Using balloon catheter injury of rat carotid artery, we showed that neointimal formation is accompanied by dramatic but transient upregulation of intimal N-cadherin and associated catenins, proteins that mediate adhesion at adherens junctions. Upregulation was demonstrated by immunofluorescence microscopy and by immunoblotting, and it coincided with evidence of phenotypic modulation of smooth muscle cells. Similar upregulation was observed when postconfluent cultures of porcine aortic smooth muscle cells were subjected to linear denuding injuries. Furthermore, treatment of wounded cultures with a blocking antibody against the extracellular domain of the N-cadherin protein significantly suppressed the repair of wounds.
N-cadherin and associated proteins are dynamically regulated during neointimal formation and provide evidence that this regulation is important for migratory repair. Therefore, N-cadherin may provide a novel target for therapies that are directed toward intimal proliferative disorders, including restenosis and vascular bypass graft failure.

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Keywords

adherens junctions
 
arterial injury
 
cell-cell adhesion
 
extracellular domain
 
functional significance
 
immunofluorescence microscopy
 
intimal N-cadherin
 
intimal proliferative disorders
 
linear denuding injuries
 
N-cadherin protein
 
novel target
 
phenotypic modulation
 
postconfluent cultures
 
rat carotid artery
 
Similar upregulation
 
Smooth muscle cell migration
 
smooth muscle cells
 
transient upregulation
 
Upregulation
 
vascular bypass graft failure
 

Mara Jones