945 TANSHINONE IIA REDUCES UROTENSIN II SIGNALING AND COMPROMISED MIGRATION IN CULTURED VASCULAR SMOOTH MUSCLE CELLS

Background: Urotensin II (UII) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as ’Danshen’ in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. In this study we examined the effect of tanshinone IIA on UII signaling and migration in VSMCs. Design and methods: VSMCs were treated with tanshinone IIA in the presence/absence of UII. Western blotting was performed to examine UII signaling. Flowcytometry was used to examine intracellular reactive oxygen species (ROS) production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay. Results: Tanshinone IIA reduced UII signaling, including phosphorylation of epidermal growth factor receptor (EGFR) and extracelluar signal-regulated kinases (ERK). Tanshinone IIA also reduced UII-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H2O2-) induced ERK activation. A further analysis indicated tanshinone IIA could inhibit UII-induced EGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that tanshinone IIA inhibited UII-induced VSMC migration. Conclusions: Our study shows that tanshinone IIA can reduce UII signaling and migration in VSMCs, suggesting a possible beneficial effect of tanshinone IIA on prevention of vascular diseases.