Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype.
Cardiovasc Res
; 75(3): 596-607, 2007 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-17531214
ABSTRACT
OBJECTIVE:
Flow-induced conversion of endothelial cells into an elongated arterial phenotype requires a coordinated regulation of cell junctions. Here we investigated the effect of acute and chronic flow on junction regulation. METHODS ANDRESULTS:
Using an extended experimental setup that allows analyses of endothelial barrier function under flow conditions, we found a flow-induced upregulation of the transendothelial electrical resistance within minutes. This was accompanied by an increase in actin filaments along the junctions and vascular endothelial (VE)-cadherin clustering, which was identified at nanoscale resolution by stimulated emission depletion microscopy. In addition, a transient tyrosine phosphorylation of VE-cadherin and catenins occurred within minutes following the onset of flow. VE-cadherin and actin distribution were maintained under chronic flow over 24 h and associated with the upregulation of VE-cadherin and alpha-catenin expression, thus compensating for the cell elongation-mediated increase in cell border length. Importantly, all observed effects were rac1 dependent as verified by the inhibitory effect of dominant negative N17rac1.CONCLUSION:
These results show that flow-induced conversion of endothelial cells into an arterial phenotype occurs while intercellular junctions remain intact. The data place rac1 in a central multimodal regulatory position that might be important in the development of vascular diseases, such as arteriosclerosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Endoteliais
/
Junções Intercelulares
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article