The Inhibitory Mechanism of YC-1, a Benzyl Indazole, on Smooth Muscle Cell Proliferation: An In Vitro and In Vivo Study

Chieh Hsi Wu, Weng Cheng Chang, Gee Yat Chang, Sheng Chu Kuo, Che Ming Teng

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26 Citations (Scopus)

Abstract

The pharmacological mechanisms of a synthetic compound 1-benzyl-3-(5′ -hydroxy-methyl-2′-furyl) indazole (YC-1) in preventing smooth muscle cell proliferation remains to be elucidated. The present study was aimed to explore the effects of YC-1 on certain molecules responsible for cell proliferation, including transforming growth factor (TGF)-β1, soluble guanylyl cyclase (sGC) and focal adhesion kinase (FAK). The in vivo assay was correlated to the in vitro results of YC-1 on vascular stenosis. YC-1 was applied topically via a pluronic gel onto the balloon-injured rat carotid arteries, which were then harvested two weeks later for histological analysis. Our in vitro results showed that TGF-β1 was suppressed by YC-1 by 50%. The translational level of sGC was threefold activated by YC-1 while the transcription level of sGC was increased up to 24-fold. FAK, the molecule responsible for cell proliferation and migration, was suppressed by YC-1 on the translational levels for 72%. These in vitro results were in consistent with the in vivo observation that the area ratio of neointima to media was reduced by YC-1. This study provides insights into the pharmacological mechanisms of YC-1 in preventing abnormal smooth muscle cell proliferation and thus supports the use of YC-1 as an adjuvant therapy for balloon injury-induced restenosis.

Original languageEnglish
Pages (from-to)252-260
Number of pages9
JournalJournal of Pharmacological Sciences
Volume94
Issue number3
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

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Keywords

  • Balloon injury
  • Restenosis
  • Soluble guanylyl cyclase
  • YC-1

ASJC Scopus subject areas

  • Pharmacology

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