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STAT3 is a positive regulator of endothelial function in the brain
Author(s) -
Davis Catherine Monica,
Young Jennifer M,
Alkayed Nabil J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb495
Subject(s) - stat3 , stat protein , ischemia , nitric oxide , western blot , endothelial dysfunction , medicine , regulator , brain ischemia , downregulation and upregulation , neuroscience , chemistry , biology , phosphorylation , microbiology and biotechnology , biochemistry , gene
Signal Transducer and Activator of Transcription 3 (STAT3) is protective to the brain following ischemic injury. The function of STAT3 in cerebral endothelial cells (ECs) in response to ischemic injury has not been investigated. Since ablation of STAT3 specifically in neurons does not alter infarct size, endothelial STAT3 may be responsible for the STAT3‐mediated protection observed in the brain. We therefore hypothesized that STAT3 protects ECs from ischemic injury. We used primary mouse cerebrovascular ECs and subjected them to oxygen and glucose deprivation (OGD), an in vitro model of ischemia. Using Western blot analysis, we found that STAT3 protein levels and phosphorylation are regulated by OGD; they are decreased immediately following OGD, increasing by 24 hours of reoxygenation to exceed pre‐OGD levels. We show that attenuation of STAT3 signaling, by pharmacological inhibition, induces EC death and reduces both nitric oxide release and trans‐endothelial electrical resistance (TEER). STAT3 is therefore a positive regulator of correct endothelial function in the brain, playing an important role in determining susceptibility to ischemic damage. Since endothelial dysfunction is a contributing factor, as well as an outcome of pathological states, regulation of endothelial STAT3 may have important consequences in cerebrovascular disease. Supported by the American Heart Association.