Effect of tranilast on extracellular matrix metalloproteinases production and no production in cultured vascular smooth muscle cells

Purpose: Tranilast, an antiallergenic drug, has been reported to reduce restenosis rate after angioplasty, but its mechanism is still unclear. Vascular smooth muscle cells (VSMC) proliferation, excessive matrix metalloproteinases (MMPs) expression and nitric oxide (NO) deficiency are thought to be key events in the development of restenosis after angioplasty. We investigated the effect of tranilast on proliferation, MMPs production, and NO production in cultured VSMC under basal and stimulated conditions. Method: Cell proliferation was evaluated by [3H]thymidine incorporation. MMPs production by VSMC were assessed by gelatin zymography. NO production by VSMC was measured by Griess reaction. Results: Tranilast (30-500/z M) did not change proliferation and MMP-2 production in quiescent VSMC. However, tranilast dose-dependently inhibited PDGFstimulated cell proliferation and PDGF-stimulated MMP-2 production. Tranilast also dose-dependently inhibited ILl/~ stimulated MMP-9 and MMP-2 productions. Moreover, tranilast increased basal and ILl/3-stimulated NO production. Conclusion: Our results suggest that prevention of restenosis after angioplasty by tranilast may be madiated by not only its antiproliferative effect but also inhibition of MMPs production and activation of NO production in VSMC.