title: Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization.
abstract: OBJECTIVE
  We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA).
  
  
  METHODS
  AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations.
  
  
  RESULTS
  Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p<0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p<0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p<0.05).
  
  
  CONCLUSIONS
  Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kaneko
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Maho
authors.initials: M
authors.lastname: Morisawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Anzai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Aoki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002122:Calcium Chloride; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; C498144:Rela protein, mouse; D013267:Stilbenes; D051996:Transcription Factor RelA; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride; D000077185:Resveratrol