Cardiovascular Pharmacology: Open Access

Li Y

Publications

• Research Article
  A Novel ASK Inhibitor AGI-1067 Inhibits TLR-4-Mediated Activation of ASK1 by Preventing Dissociation of Thioredoxin from ASK1
  Author(s): Li Y, Zheng S, Long L, Jenny Zhou H, Ji W and Min WLi Y, Zheng S, Long L, Jenny Zhou H, Ji W and Min W
  
  The cell type that normally limits the inflammatory and atherosclerotic process is the vascular Endothelial Cell (EC) that can be regulated by pro-inflammatory and various stresses. Toll-like Receptor-4 (TLR4) plays an important role in the pathogenesis of atherosclerosis, in part, by activating Apoptosis Signal-regulating Kinase 1 (ASK1) to initiate the activation of MAP kinases pathways and the expression of inflammatory genes. In the present study, we test the hypothesis that AGI-1067 acts as an anti-inflammatory agent by inhibiting the activation of ASK1 in human EC. Pretreatment of human aortic endothelial cells with AGI-1067 inhibits TLR4 ligand (LPS)-induced activation of ASK1 and the downstream p38 and c-Jun N-terminal Kinase (JNK) MAP kinases. LPS dissociate two endogenous inhibitors Thioredoxin-1 (Trx1) and 14-3-3 from ASK1, leading to ASK1 autoactivation. Interestingly, AGI.. View More»
  DOI: 10.4172/2329-6607.1000132

  Abstract PDF