Discovery of a pyrazole derivative promoting angiogenesis through modulating reactive oxygen species and interferon-inducible protein 10 levels.
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.
Wang
Maohua
M
Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, 324# Jing 5 Road, Jinan 250021, China. doctorwmh@yahoo.com.cn
Zhang
Jingyong
J
Wu
Xuejun
X
Jin
Xing
X
Zhao
Baoxiang
B
Zhang
Lu
L
Yuan
Hai
H
Zhou
Hua
H
Gao
Binbin
B
Lv
Wei
W
Kong
Xiangqian
X
Miao
Junying
J
D015153:Blotting, Western; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D011720:Pyrazoles; D017382:Reactive Oxygen Species; C530900:ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate