The indazole derivative YD-3 inhibits thrombin-induced vascular smooth muscle cell proliferation and attenuates intimal thickening after balloon injury

Chieh Yu Peng, Shiow Lin Pan, Jih Hwa Guh, Yi Nan Liu, Ya Ling Chang, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Proliferation of vascular smooth muscle cells (VSMCs) is postulated to be one of the key events in the pathogenesis of atherosclerosis and restenosis. We investigated whether YD-3, a low-molecular weight, non-peptide compound, could modulate proliferation of VSMCs in vitro and restenosis after balloon angioplasty in vivo. We examined the effect of YD-3 on thrombin-induced VSMC proliferation by [3H]thymidine incorporation assay. The data demonstrated that YD-3 inhibited VSMC proliferation in a concentration-dependent manner. To define the mechanisms of YD-3 action, we found that YD-3 showed a profound inhibition on thrombin-induced Ras and ERK1/2 activities by using Western blotting analysis. Furthermore, oral administration of YD-3 exhibited a marked reduction in neointimal thickness using the carotid injury model in rats. Using immunochemical detection, our experiments also revealed that YD-3 significantly suppressed expression of the PAR-I receptor, and markedly inhibited PAR-I-activating peptide (SFLLRN)-induced VSMC proliferation in a concentration-dependent manner. These results suggest that YD-3 inhibits thrombin-induced VSMC growth via the Ras- and ERK1/2-mediated signaling pathway. Moreover, YD-3 also shows a developmental potential in the treatment of atherosclerosis and restenosis after vascular injury.

Original languageEnglish
Pages (from-to)1232-1239
Number of pages8
JournalThrombosis and Haemostasis
Volume92
Issue number6
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Fingerprint

Indazoles
Tunica Intima
Vascular Smooth Muscle
Thrombin
Smooth Muscle Myocytes
Cell Proliferation
Wounds and Injuries
Atherosclerosis
Balloon Angioplasty
Vascular System Injuries
Thymidine
Oral Administration
Molecular Weight
Western Blotting
Peptides
Growth

Keywords

  • Restenosis
  • Signal transduction
  • Thrombin
  • Vascular smooth muscle cells
  • YD-3

ASJC Scopus subject areas

  • Hematology

Cite this

The indazole derivative YD-3 inhibits thrombin-induced vascular smooth muscle cell proliferation and attenuates intimal thickening after balloon injury. / Peng, Chieh Yu; Pan, Shiow Lin; Guh, Jih Hwa; Liu, Yi Nan; Chang, Ya Ling; Kuo, Sheng Chu; Lee, Fang Yu; Teng, Che Ming.

In: Thrombosis and Haemostasis, Vol. 92, No. 6, 12.2004, p. 1232-1239.

Research output: Contribution to journalArticle

Peng, Chieh Yu ; Pan, Shiow Lin ; Guh, Jih Hwa ; Liu, Yi Nan ; Chang, Ya Ling ; Kuo, Sheng Chu ; Lee, Fang Yu ; Teng, Che Ming. / The indazole derivative YD-3 inhibits thrombin-induced vascular smooth muscle cell proliferation and attenuates intimal thickening after balloon injury. In: Thrombosis and Haemostasis. 2004 ; Vol. 92, No. 6. pp. 1232-1239.
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