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Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro

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Abstract

Objective

To investigate the pro-angiogenic effects of paeoniflorin (PF) in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells (HUVECs).

Methods

In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg(fli-1:EGFP)y1 transgenic zebrafish. The 24 h post fertilization (hpf) embryos were pretreated with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor II (VRI) for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels (ISVs) was observed with a fluorescence microscope. The mRNA expression of fms-like tyrosine kinase-1 (flt-1), kinase insert domain receptor (kdr), kinase insert domain receptor like (kdrl) and von Willebrand factor (vWF) were analyzed by real-time polymerase chain reaction (PCR). In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed.

Results

PF (6.25–100 μmol/L) could rescue VRI-induced blood vessel loss in zebrafish and PF (25–100 μmol/L), thereby restoring the mRNA expressions of flt-1, kdr, kdrl and vWF, which were down-regulated by VRI treatment. In addition, PF (0.001–0.03 μmol/L) could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0–10 μmol/L and tube formation at 0.3 μmol/L.

Conclusion

PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.

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Correspondence to Ke-ji Chen.

Additional information

Supported by the Science and Technology Development Fund of Macao SAR (No. 078/2011/A3 and 134/2014/A3), Research Committee of University of Macau (No. MYRG2015-00182-ICMS-QRCM), and Beijing Municipal Science and Technology Commission (No. Z141100002214011), China

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Xin, Qq., Yang, Br., Zhou, Hf. et al. Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro. Chin. J. Integr. Med. 24, 494–501 (2018). https://doi.org/10.1007/s11655-016-2262-2

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