Jie Yu1, Keisuke Morimoto1, Wulan Bao1, Zhenhai Yu1, Yutaka Okita1, Kenji Okada2. 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. 2. Department of Surgery, Division of Cardiovascular Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan. yutamo@aol.com.
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.
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.
Entities:
Keywords:
Abdominal aortic aneurysm; GLP-1; Reactive oxygen species
Authors: R Pyo; J K Lee; J M Shipley; J A Curci; D Mao; S J Ziporin; T L Ennis; S D Shapiro; R M Senior; R W Thompson Journal: J Clin Invest Date: 2000-06 Impact factor: 14.808