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 β (TGFβ) 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 TGFβ 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.