title: Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.
abstract: Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression.
  
  
  
  AAA was induced with administration of intraluminal elastase and extraluminal CaCl2in male rats. Rats were randomly divided into a control group (n = 30) and an EGCG group (n = 30). In the EGCG group, an EGCG solution (20 mg/d) was administered orally to each rat from 2 weeks before AAA induction and continued 4 weeks beyond induction.
  
  
  
  The abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P < .0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4 ± 13.6 vs 46.7 ± 13.4 μm [P < .001] and 20.3 ± 4.6 vs 9.5 ± 3.6% [P < .0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P < .05], lysyl oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P < .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P < .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P < .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P < .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P < .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P < .05).
  
  
  
  EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Setozaki
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: minakata@kuhp.kyoto-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Minakata
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Masumoto
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hirao
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002122:Calcium Chloride; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010196:Pancreatic Elastase; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification; D010946:Plants, Medicinal; D059808:Polyphenols / Q000008:administration & dosage* / Q000302:isolation & purification; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013662:Tea / Q000737:chemistry*; D013997:Time Factors; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D014333:Tropoelastin; D002392:Catechin; D003094:Collagen; D004549:Elastin; C045651:epigallocatechin gallate; D008249:Protein-Lysine 6-Oxidase; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1; D002122:Calcium Chloride