1. Glucagon-like peptide-1 prevented abdominal aortic aneurysm development in rats.
- Author
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Yu, Jie, Morimoto, Keisuke, Bao, Wulan, Yu, Zhenhai, Okita, Yutaka, and Okada, Kenji
- Subjects
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GLUCAGON-like peptide-1 receptor , *AORTIC aneurysms , *PHARMACODYNAMICS , *REACTIVE oxygen species , *CELLULAR signal transduction , *IMMUNOSTAINING , *LABORATORY rats - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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