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

Fingerprint

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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