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

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)1232-1239
頁數8
期刊Thrombosis and Haemostasis
92
發行號6
DOIs
出版狀態已發佈 - 十二月 2004
對外發佈Yes

ASJC Scopus subject areas

  • Hematology

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