Document Detail

Activation of transglutaminase type 2 for aortic wall protection in a rat abdominal aortic aneurysm formation.
MedLine Citation:
PMID:  20615646     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The altered structure and composition of the vascular extracellular matrix (ECM) influences the formation of abdominal aortic aneurysms (AAA). Transglutaminase type 2 (TG2), which is a Ca(2+)-dependent cross-linking enzyme, has been proven the importance for ECM homeostasis, but there is no evidence of TG2 in AAA formation. The hypothesis was investigated that TG2 contributes to protect aortic walls during remodeling of the AAAs.
METHODS: In a rat abdominal aortic aneurysm model using a combination of intraluminal elastase infusion and extraluminal calcium chloride, TG2 expression and activity were evaluated at 1 and 8 weeks after the AAA preparation (n = 6 at each endpoint), compared with those of the non-prepared aorta (n = 6). Additionally, ex vivo experiments of isolated AAA tissue culture with recombinant human TG2, TG2 inhibitor cystamine, or tissue necrosis factor (TNF)-α were performed.
RESULTS: TG2 mRNA expression in the AAAs was significantly upregulated at both 1 and 8 weeks (22.4-fold and 5.4-fold increases of the non-prepared aorta, P = .0022 and P = .0048, respectively). TG2 protein expression and activity were also enhanced by fluorescent staining of the AAAs. Similar mRNA upregulation of TNF-α, interleukin-1β, matrix metalloproteinases (MMP)-2, MMP-9, and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was observed in the AAAs, and TG2 and TNF-α were colocalized in the aortic walls at 1 week. Ex vivo experiments showed that mRNA expressions of TNF-α, MMP-2, and MMP-9 in the cultured AAA tissue were decreased by exogenous TG2, whereas were increased by cystamine. TNF-α exposure to the AAA tissues was significantly upregulated TG2 mRNA expression (P = .0333).
CONCLUSION: TG2 expression and activity in AAA formation were enhanced, possibly due to compensatory reaction. TG2 has a potential role of ECM protector in aortic walls during remodeling of the AAAs.
Takashi Munezane; Tomomi Hasegawa; Suritala; Akiko Tanaka; Kenji Okada; Yutaka Okita
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Publication Detail:
Type:  Journal Article     Date:  2010-07-07
Journal Detail:
Title:  Journal of vascular surgery     Volume:  52     ISSN:  1097-6809     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-28     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  967-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Society for Vascular Surgery. All rights reserved.
Department of Surgery, Division of Cardiovascular Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
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MeSH Terms
Aorta, Abdominal / drug effects,  enzymology*
Aortic Aneurysm, Abdominal / chemically induced,  enzymology,  genetics,  prevention & control*
Calcium Chloride
Cystamine / pharmacology
Disease Models, Animal
Enzyme Activation
Enzyme Inhibitors / pharmacology
GTP-Binding Proteins / antagonists & inhibitors,  genetics,  metabolism*
Gene Expression Regulation, Enzymologic
Inflammation Mediators / metabolism
Interleukin-1beta / genetics
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 9 / genetics
Pancreatic Elastase
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Recombinant Proteins / metabolism
Time Factors
Tissue Culture Techniques
Tissue Inhibitor of Metalloproteinase-1 / genetics
Tissue Inhibitor of Metalloproteinase-2 / genetics
Transglutaminases / antagonists & inhibitors,  genetics,  metabolism*
Tumor Necrosis Factor-alpha / genetics,  metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Interleukin-1beta; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Tumor Necrosis Factor-alpha; 10043-52-4/Calcium Chloride; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 51-85-4/Cystamine; EC 2.3.2.-/transglutaminase 2; EC; EC transglutaminase 2, human; EC Elastase; EC Metalloproteinase 2; EC protein, rat; EC Metalloproteinase 9; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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