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Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis

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Abstract

Serum amyloid A (SAA), a major acute-phase reactant, modulates angiogenesis in many diseases. Vascular endothelial growth factor receptor 2 (VEGFR2) is the primary angiogenic receptor for vascular endothelial growth factor (VEGF), but the possibility of an interaction between SAA and VEGFR2 has not yet been resolved. Here, we investigated if SAA stimulates the expression of VEGFR2 and promotes angiogenesis in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant SAA (rSAA), and the messenger RNA (mRNA) and protein expression of VEGFR2 was detected by Western blot analysis and quantitative real-time PCR. Formyl peptide receptor–like 1 (FPRL1) agonist (WKYMVm) and antagonist (WRW4) and inhibitors of mitogen-activated protein kinases (MAPKs) were used to investigate the mechanism of regulation of VEGFR2.We show that SAA induces VEGFR2 expression in a time- and dose-dependent manner in HUVECs. In addition, SAA promotes tube formation in HUVECs. The effect of SAA on tube formation was shown to be the result of an increase in VEGFR2 expression, which was blocked by the multi-angiokinase receptor inhibitor BIBF1120. These activities of SAA appear to be mediated by FPRL1/MAPK signaling pathways, as they were mimicked by WKYMVm and abrogated by WRW4 and inhibitors of MAPKs. These observations indicate that SAA induces VEGFR2 expression and promotes tube formation in HUVECs via the FPRL1/MAPK signaling pathway, thus providing a potential target for the control of angiogenesis.

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Acknowledgments

The authors acknowledge the Key Laboratory of Cardiovascular Remodeling and Function Research in Qilu Hospital of Shandong University for its kind provision of equipments and materials. We thank the Natural Science Foundation of China (no. 26010105131336) for its funding support.

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Authors and Affiliations

  1. Qilu Hospital of Shandong University, Ji’nan, Shandong, 250012, People’s Republic of China

    Mei Lv, Bo Li, Hui Liu, Jin-yu Pan, Bei-bei Li, Cheng Zhang & Feng-shuang An

  2. Department of Ultrasound, Shandong Provincial Hospital, Ji’nan, People’s Republic of China

    Yan-fei Xia

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  1. Mei Lv
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  2. Yan-fei Xia
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  3. Bo Li
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  4. Hui Liu
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  7. Cheng Zhang
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Correspondence to Feng-shuang An.

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Lv, M., Xia, Yf., Li, B. et al. Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis. J Physiol Biochem 72, 71–81 (2016). https://doi.org/10.1007/s13105-015-0462-4

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  • DOI: https://doi.org/10.1007/s13105-015-0462-4

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