Taketoshi Yamazaki

Circulating matrix metalloproteinase-2 is elevated in patients with congestive heart failure.

It has been reported that matrix metalloproteinase (MMP) protein concentration and activity are upregulated in the failing human heart. However, there are few reports describing the role of elevated level of circulating MMPs in congestive heart failure (CHF) patients. This study examined whether circulating matrix metalloproteinases (MMPs) are also related to the pathogenesis of CHF.

Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure: MMP-9 predicts HF events

Matrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF.

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.