STAT1 as a novel therapeutical target in pro-atherogenic signal integration of IFNγ, TLR4 and IL-6 in vascular disease

Consequently, STAT1 has been identified as a point of convergence for the cross-talk between the pro-atherogenic IFN-γ, TLR4 and IL-6 activated pathways in immune as well as vascular cells, as such amplifying pro-inflammatory signals. This results in augmented smooth muscle cell (SMC) and leukocyte migration, leukocyte to endothelial cell (EC) adhesion and foam cell formation, and could encompass a novel mechanism involved in the initiation and progression of atherosclerosis. Therefore, application of small inhibitory compounds that specifically interact with the SH2-phosphotyrosine pocket of STAT1, proposed here as a novel working mechanism for the known STAT1 inhibitor fludarabine, could be a promising tool in the development of a therapeutical strategy for atherosclerosis.