Document Detail

Inhibition of Development of Abdominal Aortic Aneurysm by Glycolysis Restriction.
MedLine Citation:
PMID:  22499992     Owner:  NLM     Status:  Publisher    
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. METHODS AND 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 analogue 18 fluoro-deoxyglucose 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.
Toshihiro Tsuruda; Kinta Hatakeyama; Shigeki Nagamachi; Yoko Sekita; Sumiharu Sakamoto; George J Endo; Masanori Nishimura; Masakazu Matsuyama; Koichi Yoshimura; Yuko Sato; Toshio Onitsuka; Takuroh Imamura; Yujiro Asada; Kazuo Kitamura
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-12
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Departments of Internal Medicine, Circulatory and Body Fluid Regulation.
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