title: Glucagon-like peptide-1 prevented abdominal aortic aneurysm development in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: 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.
authors.forename: Wulan
authors.initials: W
authors.lastname: Bao
authors.affiliation: 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.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okita
authors.affiliation: Department of Surgery, Division of Cardiovascular Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan. yutamo@aol.com.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okada
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000502:physiology; D007279:Injections, Subcutaneous; D008297:Male; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D017382:Reactive Oxygen Species; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: Abdominal aortic aneurysm; GLP-1; Reactive oxygen species