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

Research output: Contribution to journalArticle

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

Fingerprint

Indazoles
Thrombin
PAR-1 Receptor
Endothelial Cells
Cell Proliferation
PAR-2 Receptor
Umbilicus
Vascular Endothelial Growth Factor Receptor-2
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
In Vitro Techniques
Thymidine
Vascular Endothelial Growth Factor A
Cell Movement
Western Blotting
Phosphorylation

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., ... 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

The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo. / Peng, Chieh Yu; Pan, Shiow Lin; Pai, Hui Chen; Tsai, An Chi; Guh, Jih Hwa; Chang, Ya Ling; Kuo, Sheng Chu; Lee, Fang Yu; Teng, Che Ming.

In: Shock, Vol. 34, No. 6, 12.2010, p. 580-585.

Research output: Contribution to journalArticle

Peng, CY, Pan, SL, Pai, HC, Tsai, AC, Guh, JH, Chang, YL, Kuo, SC, Lee, FY & Teng, CM 2010, 'The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo', Shock, vol. 34, no. 6, pp. 580-585. https://doi.org/10.1097/SHK.0b013e3181df00a3
Peng, Chieh Yu ; Pan, Shiow Lin ; Pai, Hui Chen ; Tsai, An Chi ; Guh, Jih Hwa ; Chang, Ya Ling ; Kuo, Sheng Chu ; Lee, Fang Yu ; Teng, Che Ming. / The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo. In: Shock. 2010 ; Vol. 34, No. 6. pp. 580-585.
@article{09fec2043bca498d83dc7d61e16a6bed,
title = "The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo",
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.",
keywords = "angiogenesis, Flk-1, human umbilical vein endothelial cells, thrombin, YD-3",
author = "Peng, {Chieh Yu} and Pan, {Shiow Lin} and Pai, {Hui Chen} and Tsai, {An Chi} and Guh, {Jih Hwa} and Chang, {Ya Ling} and Kuo, {Sheng Chu} and Lee, {Fang Yu} and Teng, {Che Ming}",
year = "2010",
month = "12",
doi = "10.1097/SHK.0b013e3181df00a3",
language = "English",
volume = "34",
pages = "580--585",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo

AU - Peng, Chieh Yu

AU - Pan, Shiow Lin

AU - Pai, Hui Chen

AU - Tsai, An Chi

AU - Guh, Jih Hwa

AU - Chang, Ya Ling

AU - Kuo, Sheng Chu

AU - Lee, Fang Yu

AU - Teng, Che Ming

PY - 2010/12

Y1 - 2010/12

N2 - 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.

AB - 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.

KW - angiogenesis

KW - Flk-1

KW - human umbilical vein endothelial cells

KW - thrombin

KW - YD-3

UR - http://www.scopus.com/inward/record.url?scp=78649631367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649631367&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e3181df00a3

DO - 10.1097/SHK.0b013e3181df00a3

M3 - Article

C2 - 20351626

AN - SCOPUS:78649631367

VL - 34

SP - 580

EP - 585

JO - Shock

JF - Shock

SN - 1073-2322

IS - 6

ER -