Upregulation of thromboxane synthase mediates visfatin-induced interleukin-8 expression and angiogenic activity in endothelial cells.

Abstract Thromboxane synthase (TXAS) is an enzyme that catalyzes the synthesis of thromboxane A 2 (TXA 2 ). Overexpression of TXAS is associated with a variety of vascular diseases. Recently, we reported that visfatin, a novel adipokine, exhibits angiogenic actions. In this study, we showed that visfatin increased mRNA and protein levels of TXAS and stimulated TXA 2 biosynthesis in vascular endothelial cells. In addition, visfatin induced the expression and secretion of interleukin-8 (IL-8), which is blocked by a TXAS inhibitor and by the transfection of siRNA specific for TXAS. Furthermore, the inhibition of TXAS activity and blockade of the IL-8 receptor attenuated visfatin-induced endothelial angiogenesis. Together, these results showed that visfatin promoted IL-8 production by upregulation of TXAS, leading to angiogenic activation in endothelial cells.