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Glucagon-like peptide-1 prevented abdominal aortic aneurysm development in rats

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Abstract

Purpose

To demonstrate the protective effect of glucagon-like peptide 1 (GLP-1) signaling on the cardiovascular system, we conducted this study to show that the GLP-1 receptor analog (lixisenatide) could inhibit abdominal aortic aneurysm (AAA) development in rats.

Methods

Lixisenatide was injected subcutaneously 7 days after aneurysm preparation. We evaluated reactive oxygen species (ROS) expression by dihydroethidium staining and 8-hydroxydeoxyguanosine (8-OHdG; the oxidation product of DNA) by immunohistochemical staining. We also analyzed the effect of GLP-1 signaling on the inflammatory response. Histopathological examination was done on day 28, and the AAA dilatation ratio was calculated.

Results

On day 14, ROS expression and 8-OHdG-positive cells in the aneurysm walls were seen to have been significantly decreased by lixisenatide treatment. Western blot analysis showed decreased ERK expression. There was significantly reduced tumor necrosis factor-α mRNA expression in the aneurysm walls and CD68-positive cell infiltration in the aneurysm walls. On day 28, it was evident that the lixisenatide had dramatically reduced aneurysm development in the rats.

Conclusion

GLP-1 elevation inhibits AAA development in rats through its anti-oxidant and anti-inflammatory effects. Thus, GLP-1 could be a potent pharmacological target for AAA treatment.

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (C) (No. 24592064) from the Japan Society for the Promotion of Science. We thank Sanofi K.K. Corporation for providing the lixisenatide. We also thank Atsumi Katsuta for assistance performing data analysis.

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Authors and Affiliations

  1. Department of Surgery, Division of Cardiovascular Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan

    Jie Yu, Keisuke Morimoto, Wulan Bao, Zhenhai Yu & Yutaka Okita

  2. Department of Surgery, Division of Cardiovascular Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan

    Kenji Okada

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  1. Jie Yu
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  2. Keisuke Morimoto
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Correspondence to Kenji Okada.

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Yu, J., Morimoto, K., Bao, W. et al. Glucagon-like peptide-1 prevented abdominal aortic aneurysm development in rats. Surg Today 46, 1099–1107 (2016). https://doi.org/10.1007/s00595-015-1287-z

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  • DOI: https://doi.org/10.1007/s00595-015-1287-z

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