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

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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.

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Abbreviations

PAOD:

Peripheral arterial occlusive disease

VECs:

Vascular endothelial cells

MPD:

Ethyl 3-(o-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate

FGF-2:

Fibroblast growth factor-2

ROS:

Reactive oxygen species

IP-10:

Interferon-inducible protein 10

HUVECs:

Human umbilical vein endothelial cells

FBS:

Fetal bovine serum

DMSO:

Dimethyl sulfoxide

NIH:

National Institutes of Health

DCHF:

2’,7’-Dichlorodihydrofluorescein

DCF:

2’,7’-Dichlorofluorescein

HRP:

Horseradish peroxidase

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was financially supported by the National 973 Research Project (No. 2006CB503803) and National Natural Science Foundation of China (No. 90813022) and the science and technology developmental project of Shandong Province (2008GG10002034 and 2007GG20002004).

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Authors and Affiliations

  1. Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, 324#, Jing 5 Road, Jinan, 250021, China

    Maohua Wang, Jingyong Zhang, Xuejun Wu, Xing Jin, Hai Yuan, Hua Zhou, Binbin Gao, Wei Lv & Xiangqian Kong

  2. Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China

    Baoxiang Zhao

  3. Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China

    Lu Zhang & Junying Miao

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  1. Maohua Wang
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Correspondence to Xing Jin, Baoxiang Zhao or Junying Miao.

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Maohua Wang and Jingyong Zhang contributed equally to this work.

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Wang, M., Zhang, J., Wu, X. et al. Discovery of a pyrazole derivative promoting angiogenesis through modulating reactive oxygen species and interferon-inducible protein 10 levels. Mol Biol Rep 38, 1491–1497 (2011). https://doi.org/10.1007/s11033-010-0256-2

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