Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tranilast has been reported to reduce restenosis rate after angioplasty, but its mechanism is still unclear. We investigated the effect of tranilast against platelet-derived growth factor (PDGF) in PDGF's proliferative effect and PDGF's inhibitory effect on cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells (VSMC). NO production was measured by Griess reaction. NO synthase (NOS) protein was evaluated by Western blot with monoclonal anti-rat inducible NOS antibody. A combination of interleukin-1 beta (IL-1 beta 1 ng/ml), tumor necrosis factor-alpha (TNF-alpha 2,000 U/ml), and lipopolysaccharide (100 ng/ml) significantly increased NO production and NOS protein, and tranilast significantly enhanced both in a dose-dependent manner. PDGF (100 ng/ml) significantly reduced both cytokine-induced NO production and NOS protein induction, but tranilast completely abolished these inhibitory effects. In the presence of cytokines, serum-stimulated cell proliferation was significantly inhibited by cytokine-induced NO, whereas PDGF-stimulated proliferation was not. On the other hand, tranilast not only inhibited the proliferative effect of PDGF directly, but also restored cytokine-induced NO production and its antiproliferative effect in the presence of PDGF.
J Cardiovasc Pharmacol 1996 Aug
PMID:Tranilast restores cytokine-induced nitric oxide production against platelet-derived growth factor in vascular smooth muscle cells. 885 74

Tranilast is clinically indicated for the treatment of allergic disorders and is also a nonselective blocker of the transient receptor potential vanilloid 2 (TRPV2) channel. Previous studies have found that it has protective effects in various animal models of cardiac disease. Our laboratory has found that genetic deletion of TRPV2 results in a blunted hypertrophic response to increased afterload; thus, this study tested the hypothesis that tranilast through cardiomyocyte TRPV2 blockade can inhibit the hypertrophic response to pressure overload in vivo through transverse aortic constriction and ex vivo through isolated myocyte studies. The in vivo studies demonstrated that tranilast blunted the fibrotic response to increased afterload and, to a lesser extent, the hypertrophic response. After 4 weeks, this blunting was associated with improved cardiac function, although at 8 weeks, the cardiac function deteriorated similarly to the control group. Finally, the in vitro studies demonstrated that tranilast was not inhibiting these responses at the cardiomyocyte level. In conclusion, we demonstrated that tranilast blunting of the fibrotic and hypertrophic response occurs independently of cardiac TRPV2 channels and may be cardioprotective in the short term but not after prolonged administration.
J Cardiovasc Pharmacol 2018 07
PMID:Tranilast Blunts the Hypertrophic and Fibrotic Response to Increased Afterload Independent of Cardiomyocyte Transient Receptor Potential Vanilloid 2 Channels. 2968 11