Discovery of a pyrazole derivative promoting angiogenesis through modulating reactive oxygen species and interferon-inducible protein 10 levels

Mol Biol Rep. 2011 Mar;38(3):1491-7. doi: 10.1007/s11033-010-0256-2. Epub 2010 Sep 15.

Abstract

Human umbilical cord vascular endothelial cells (HUVECs) cultured without serum and fibroblast growth factor-2 is an in vitro model of ischemic conditions. Our previous study showed that ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (MPD) could inhibit apoptosis of HUVECs in this model. In this study, we investigated the effect of MPD on angiogenesis and the possible mechanisms. Capillary-like tube formation assay on Matrigel and cell migration assay were performed to investigate the effect of MPD on angiogenesis. The reactive oxygen species (ROS) and interferon-inducible protein 10 (IP-10) levels were respectively evaluated by intracellular ROS assay and western blot analysis. MPD at 5 and 10 μM promoted vascular structure formation and HUVEC migration in an in vitro ischemic model. MPD promoted angiogenesis through elevating ROS levels and depressing IP-10 level. ROS seemed to be necessary for angiogenesis, and a high level of IP-10 inhibited angiogenesis in ischemic state. ROS provide clues for seeking new key factors involved in angiogenesis. IP-10 may become a new target for future therapeutic intervention. MPD is a good tool for investigating the mechanism of angiogenesis, and MPD might be useful in the development of new drugs in therapy of ischemic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Capillaries / cytology
  • Capillaries / drug effects
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Chemokine CXCL10 / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Umbilical Veins / cytology

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10
  • Pyrazoles
  • Reactive Oxygen Species
  • ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate