Inhibitory effects of trapidil on PDGF signaling in balloon-injured rat carotid artery

Jun o. Deguchi, Jun ichi Abe, Masatoshi Makuuchi, Yoh Takuwa

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Trapidil, which was originally developed as an anti-platelet agent, is among the few agents thus far proven to be clinically effective in preventing restenosis after percutaneous coronary interventions. Trapidil was previously shown to inhibit platelet-derived growth factor (PDGF)-induced cellular responses in vitro in cultured cells. However, its mechanism of action is poorly understood. In this study, we investigated by using a rat carotid balloon-injury model whether and how trapidil inhibited the in vivo action of PDGF, which is regarded as a most important growth factor implicated in proliferation and migration of vascular smooth muscle cells. The combination of both oral and topical administration of trapidil reduced the intimal lesion size by more than 70 % and nearly completely suppressed injury-induced increases in phosphotyrosine content of PDGF α- and β- receptors of carotid artery. Moreover, trapidil was found to decrease mRNA levels of PDGF α- and β- receptors strongly and of PDGF A- and B- chains moderately in injured arteries. These results indicate that trapidil potently suppresses the action of PDGF with inhibition of neointima formation in injured artery, which is mediated at least in part through decreasing the expression of both PDGF ligands and their receptors.

Original languageEnglish (US)
Pages (from-to)2791-2799
Number of pages9
JournalLife Sciences
Volume65
Issue number26
DOIs
StatePublished - Nov 19 1999
Externally publishedYes

Keywords

  • Balloon injury
  • Neointima
  • PDGF
  • Trapidil
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)

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