Literature DB >> 19893320

Transglutaminase 2 deficiency decreases plaque fibrosis and increases plaque inflammation in apolipoprotein-E-deficient mice.

Jozef L Van Herck1, Dorien M Schrijvers, Guido R Y De Meyer, Wim Martinet, Cor E Van Hove, Hidde Bult, Christiaan J Vrints, Arnold G Herman.   

Abstract

AIM: Transglutaminase 2 (TG2) is important for the deposition and stability of the extracellular matrix via effects on cross-linking of matrix proteins and transforming growth factor beta (TGFbeta) activity. The purpose of this study was to investigate the effect of TG2 deficiency on the composi- tion of atherosclerotic plaques.
METHODS: Apolipoprotein E (ApoE)(-/-) mice were crossbred with TG2(-/-) mice to obtain ApoE(-/-)TG2(-/-) mice. ApoE(-/-) and ApoE(-/-)TG2(-/-) mice were fed a Western-type diet for 16 or 30 weeks to determine the effect of TG2 deficiency on early and advanced atherosclerosis, respectively.
RESULTS: Atherosclerotic plaques of ApoE(-/-)TG2(-/-) mice showed decreased cross-linking of matrix proteins, as well as decreased nuclear staining for phospho-Smad2/-Smad3, indicative of decreased TGFbeta activity. Compared to ApoE(-/-) mice, plaque area was decreased by 45 and 48% in ApoE(-/-)TG2(-/-) mice after 16 and 30 weeks, respectively. Sirius red staining showed a significant decrease in collagen content in early and advanced atherosclerotic plaques of ApoE(-/-)TG2(-/-) mice. Furthermore, there was a significant increase in macrophages in advanced atherosclerotic plaques of ApoE(-/-)TG2(-/-) mice.
CONCLUSION: TG2 deficiency resulted in a decreased collagen content and increased inflammation, which are features of a more unstable plaque. Copyright 2009 S. Karger AG, Basel.

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Year:  2009        PMID: 19893320     DOI: 10.1159/000255966

Source DB:  PubMed          Journal:  J Vasc Res        ISSN: 1018-1172            Impact factor:   1.934


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