XXXX and CRAC channel dependence of @entity7 -activated Ca2+ entry and endothelial tube formation.

@entity1 @entity59119 @entity7 @entity7010 @entity23128 @entity1573 @entity7011 @entity460 @entity18811
RATIONALE: @entity7011 and the associated @entity460 release-activated @entity460 (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown. OBJECTIVE: The aim of this study was to investigate the relevance of @entity7011 and CRAC channels to @entity7 ( @entity7 ) and endothelial tube formation. METHODS AND RESULTS: In @entity1 umbilical vein endothelial cells, @entity7011 disruption by short-interfering RNA or dominant-negative mutant @entity7011 inhibited @entity460 release-activated (store-operated) @entity460 entry, @entity7 -evoked @entity460 entry, cell migration, and in vitro tube formation. Expression of exogenous wild-type @entity7011 rescued the tube formation. @entity7 receptor-2 and @entity7011 partially colocalized. @entity7011 disruption also inhibited @entity460 entry and tube formation in endothelial progenitor cells from @entity1 blood. A known blocker of the immune cell CRAC channel ( @entity59119 (2',5'-dimethoxybiphenyl-4-yl)amide) was a strong blocker of store-operated @entity460 entry in endothelial cells and inhibited @entity460 entry evoked by @entity7 in 3 types of @entity1 endothelial cell. The compound lacked effect on @entity7 -evoked @entity460 -release, @entity7010 clustering, and 2 types of transient receptor potential channels, @entity18811 and @entity23128 . Without effect on cell viability, the compound inhibited @entity1 endothelial cell migration and tube formation in vitro and suppressed angiogenesis in vivo in the @entity1573 chorioallantoic membrane. The compound showed 100-fold greater potency for endothelial compared with immune cell @entity460 entry. CONCLUSIONS: The data suggest positive roles for @entity7011 and CRAC channels in @entity7 -evoked @entity460 entry and new opportunity for chemical modulation of angiogenesis.
