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

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.

journal_name

J Vasc Res

authors

Van Herck JL,Schrijvers DM,De Meyer GR,Martinet W,Van Hove CE,Bult H,Vrints CJ,Herman AG

doi

10.1159/000255966

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

231-40

issue

3

eissn

1018-1172

issn

1423-0135

pii

000255966

journal_volume

47

pub_type

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