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

Autor: Maohua Wang, Jingyong Zhang, Xuejun Wu, Xing Jin, Baoxiang Zhao, Lu Zhang, Hai Yuan, Hua Zhou, Binbin Gao, Wei Lv, Xiangqian Kong, Junying Miao
Zdroj: Molecular Biology Reports; Mar2011, Vol. 38 Issue 3, p1491-1497, 7p, 2 Color Photographs, 1 Diagram, 4 Graphs
Abstrakt: 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-1 H-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index