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

Research output: Contribution to journalArticle

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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Indazoles
Smooth Muscle Myocytes
Cell Proliferation
Focal Adhesion Protein-Tyrosine Kinases
Transforming Growth Factors
Benzyl Compounds
Pharmacology
Poloxamer
Neointima
Carotid Arteries
Cell Movement
Blood Vessels
Pathologic Constriction
Gels
Observation
In Vitro Techniques
Wounds and Injuries
Soluble Guanylyl Cyclase

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

The Inhibitory Mechanism of YC-1, a Benzyl Indazole, on Smooth Muscle Cell Proliferation : An In Vitro and In Vivo Study. / Wu, Chieh Hsi; Chang, Weng Cheng; Chang, Gee Yat; Kuo, Sheng Chu; Teng, Che Ming.

In: Journal of Pharmacological Sciences, Vol. 94, No. 3, 03.2004, p. 252-260.

Research output: Contribution to journalArticle

Wu, Chieh Hsi ; Chang, Weng Cheng ; Chang, Gee Yat ; Kuo, Sheng Chu ; Teng, Che Ming. / The Inhibitory Mechanism of YC-1, a Benzyl Indazole, on Smooth Muscle Cell Proliferation : An In Vitro and In Vivo Study. In: Journal of Pharmacological Sciences. 2004 ; Vol. 94, No. 3. pp. 252-260.
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