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Immunohistochemical study of the growth factors, aFGF, bFGF, PDGF-AB, VEGF-A and its receptor (Flk-1) during arteriogenesis

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Abstract

Growth factors are viewed as main arteriogenic stimulators for collateral vessel growth. However, the information about their native expression and distribution in collateral vessels is still limited. This study was designed to profile expression of acidic and basic FGF, platelet-derived growth factor (PDGF-AB) and vascular endothelial growth factor (VEGF-A) and its receptor, fetal liver kinase-1 (Flk-1) during arteriogenesis by confocal immunofluorescence in both dog ameroid constrictor model and rabbit arteriovenous shunt model of arteriogenesis. We found that: (1) in normal arteries (NA) in dog heart, aFGF, bFGF, and PDGF-AB all were mainly expressed in endothelial cells (EC) and media smooth muscle cells (SMC), but the expression of aFGF was very weak, with those of the other two being moderate; (2) in collateral arteries (CAs), aFGF, bFGF, and PDGF-AB all were significantly upregulated (P < 0.05); they were present in all the layers of the vascular wall and were 2.1, 1.7, and 1.9 times higher than that in NA, respectively; and (3) in NA in rabbit hind limb, VEGF-A was absent, Flk-1 was only weakly present in endothelial cells, but in one week CAs VEGF-A and Flk-1 were significantly increased in both shunt and ligation sides; this was more evident in the shunt-side CAs, 2.3, and 2 times higher than that in the ligation side, respectively. In conclusion, our data demonstrate for the first time that growth factors, aFGF, bFGF, and PDGF-AB are significantly upregulated in collateral vessels in dog heart, and enhanced VEGF-A and its receptor, Flk-1, are associated with rapid and lasting increased shear stress. These findings suggest that endogenous production of growth factors could be an important factor promoting collateral vessel growth.

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Acknowledgements

This study was partly supported by the NSFC of Chinese government (Nos. 30771134 and 30971532), and by the (non-profit) Kuehl Foundation of Germany.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, 172 Tong-Zhi-Po Road, Changsha, Hunan, 410078, People’s Republic of China

    Xiaoqiong Wu, Wu Zhu & Wei-Jun Cai

  2. Department of Orthopedics, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

    Song Wu

  3. Max-Planck-Institute for Heart and Lung Research, Arteriogenesis Research Group, Parkstr. 1, 61231, Bad Nauheim, Germany

    Jutta Schaper & Wolfgang Schaper

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  1. Song Wu
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  2. Xiaoqiong Wu
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  3. Wu Zhu
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  4. Wei-Jun Cai
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Correspondence to Wei-Jun Cai, Jutta Schaper or Wolfgang Schaper.

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Wu, S., Wu, X., Zhu, W. et al. Immunohistochemical study of the growth factors, aFGF, bFGF, PDGF-AB, VEGF-A and its receptor (Flk-1) during arteriogenesis. Mol Cell Biochem 343, 223–229 (2010). https://doi.org/10.1007/s11010-010-0517-3

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