Tranilast restores cytokine-induced nitric oxide production against platelet-derived growth factor in vascular smooth muscle cells

Keiichi Hishikawa, Toshio Nakaki, Junichi Hirahashi, Takeshi Marumo, Takao Saruta

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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-1β (IL-1β 1 ng/ml), tumor necrosis factor-α (TNF-α 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.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume28
Issue number2
DOIs
Publication statusPublished - 1996 Oct 7

Keywords

  • Atherosclerosis
  • Nitric oxide
  • Platelet-derived growth factor synthase
  • Restenosis

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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