The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo

Chieh Yu Peng, Shiow Lin Pan, Hui Chen Pai, An Chi Tsai, Jih Hwa Guh, Ya Ling Chang, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

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4 Citations (Scopus)

Abstract

Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and the inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to examine the antiangiogenic efficacy of YD-3 [1-benzyl- 3(ethoxycarbonylphenyl)-indazole], a selective thrombin inhibitor, on thrombin-induced endothelial cell proliferation and neoangiogenesis in a murine Matrigel model. First, the effect of YD-3 on angiogenesis was evaluated in vivo using the mouse Matrigel implant model. Plugs treated with 1 and 10 μM of YD-3 inhibited neovascularization induced by thrombin, protease-activated receptor (PAR) 1, and PAR-4, but not by vascular endothelial growth factor, in a concentration-dependent manner over 7 days. These results indicate that YD-3 has specific antiangiogenic activity on thrombin. YD-3 also inhibited (in a concentration-dependent manner) the ability of thrombin, PAR-1, and PAR-4, but not PAR-2, to induce the proliferation of human umbilical vascular endothelial cells, using a [3H]thymidine incorporation assay. YD-3 predominantly inhibited thrombin-induced vascular endothelial growth factor receptor 2 (Flk-1) expression, but not extracellular signal-regulated kinase 1/2 phosphorylation, using Western blot analysis. YD-3 may have benefit in elucidating pathophysiology induced by thrombin-induced angiogenesis.

Original languageEnglish
Pages (from-to)580-585
Number of pages6
JournalShock
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 2010

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Keywords

  • angiogenesis
  • Flk-1
  • human umbilical vein endothelial cells
  • thrombin
  • YD-3

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Peng, C. Y., Pan, S. L., Pai, H. C., Tsai, A. C., Guh, J. H., Chang, Y. L., Kuo, S. C., Lee, F. Y., & Teng, C. M. (2010). The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo. Shock, 34(6), 580-585. https://doi.org/10.1097/SHK.0b013e3181df00a3