miR-155 Regulated Inflammation Response by the SOCS1-STAT3-PDCD4 Axis in Atherogenesis

Inflammation response plays a critical role in all phases of atherosclerosis (AS). Increased evidence has demonstrated that miR-155 mediates inflammatory mediators in macrophages to promote plaque formation and rupture. However, the precise mechanism of miR-155 remains unclear in AS. Here, we also found that miR-155 and PDCD4 were elevated in the aortic tissue of atherosclerotic mice and ox-LDL treated RAW264.7 cells. Further studies showed that miR-155 not only directly inhibited SOCS1 expression, but also increased the expression of p-STAT and PDCD4, as well as the production of proinflammation mediators IL-6 and TNF-alpha. Downregulation of miR-155 and PDCD4 and upregulation of SOCS1 obviously decreased the IL-6 and TNF-alpha expression. In addition, inhibition of miR-155 levels in atherosclerotic mice could notably reduce the IL-6 and TNF-alpha. level in plasma and aortic tissue, accompanied with increased p-STAT3 and PDCD4 and decreased SOCS1. Thus, miR-155 might mediate the inflammation in AS via the SOCS1-STAT3-PDCD4 axis. These results provide a rationale for intervention of intracellular miR-155 as possible antiatherosclerotic targets.