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Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model

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Abstract

Purpose

Angiogenesis is an essential process in liver regeneration. Nitric oxide (NO) and vascular endothelial growth factor (VEGF) are the main regulators of normal and pathological angiogenesis. This study aimed to determine the roles of NO derived from endothelial nitric oxide synthase (eNOS) and VEGF in sinusoidal endothelial cell (SEC) proliferation during liver regeneration.

Methods

Sprague-Dawley rats underwent a 70% partial hepatectomy (PHx), and were euthanized 0, 24, 48, 72, or 168 h later. Liver regeneration and SEC proliferation were evaluated. The protein expression of VEGF and eNOS was examined by a Western blot analysis. The rats were also treated with the NO synthase inhibitor N G-nitro-l-arginine-methyl ester (L-NAME) to examine its effects on liver regeneration and SEC proliferation.

Results

The proliferating cell nuclear antigen (PCNA) labeling index of hepatocytes was significantly increased at 24 h after PHx. The eNOS protein expression and NO production were significantly increased from 72 to 168 h. The expression of VEGF protein was significantly increased at 72 h. L-NAME significantly inhibited the increases in the liver mass and decreased the PCNA labeling index of hepatocytes at 24 h. L-NAME also inhibited the induction of VEGF protein at 72 h.

Conclusions

Endothelial NOS and VEGF coordinately regulate SEC proliferation during liver regeneration. Sinusoidal endothelial cell proliferation is necessary and is an important step in liver regeneration.

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Authors and Affiliations

  1. Department of Disaster and Emergency Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Daisuke Yoshida & Makoto Hashizume

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Daisuke Yoshida, Tomohiko Akahoshi, Hirofumi Kawanaka, Shohei Yamaguchi, Nao Kinjo, Akinobu Taketomi, Morimasa Tomikawa, Ken Shirabe & Yoshihiko Maehara

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  1. Daisuke Yoshida
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Yoshida, D., Akahoshi, T., Kawanaka, H. et al. Roles of vascular endothelial growth factor and endothelial nitric oxide synthase during revascularization and regeneration after partial hepatectomy in a rat model. Surg Today 41, 1622–1629 (2011). https://doi.org/10.1007/s00595-010-4484-9

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  • DOI: https://doi.org/10.1007/s00595-010-4484-9

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