Abstract
results: EBF, measured by transendothelial electrical resistance, was impaired in HAEC with SRL treatment or transfection with siRNA for FKBP12.6. This impairment was reversed when pretreated with ryanodine, a stabilizer of RyR2 Ca2+ release channels. Intracellular Ca2+ increased in HAEC treated with SRL and normalized with ryanodine. HAEC treated with SRL demonstrated increases in PKCalpha phosphorylation, a serine/threonine kinase important in VE cadherin barrier function through its interaction with p120-catenin. Immunostaining of both HAEC and MAE showed disruption of VE cadherin (green) and p120 (red) in cells/aortas treated with SRL (igure). SRL impairment of EBF was abolished by HAEC transfection with PKCalpha siRNA. Mice treated with SRL demonstrated increased MAE permeability measured by Evans blue.
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