title: Inhibition of development of abdominal aortic aneurysm by glycolysis restriction.
abstract: OBJECTIVE
  The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development.
  
  
  RESULTS
  Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl(2) in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells.
  
  
  CONCLUSIONS
  This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.
authors.affiliation: Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara Kiyotake, Miyazaki 889-1692, Japan. ttsuruda@med.miyazaki-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tsuruda
authors.forename: Kinta
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nagamachi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sekita
authors.forename: Sumiharu
authors.initials: S
authors.lastname: Sakamoto
authors.forename: George J
authors.initials: GJ
authors.lastname: Endo
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishimura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshio
authors.initials: T
authors.lastname: Onitsuka
authors.forename: Takuroh
authors.initials: T
authors.lastname: Imamura
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D015153:Blotting, Western; D002122:Calcium Chloride; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D019788:Fluorodeoxyglucose F18; D000804:Angiotensin II; D003847:Deoxyglucose; D020780:Matrix Metalloproteinase 9; D002122:Calcium Chloride; D013755:Tetradecanoylphorbol Acetate