Effect of transglutaminase 2 (TG2) deficiency on atherosclerotic plaque stability in the apolipoprotein E deficient mouse.
BACKGROUND
Transglutaminase 2 (TG2), a cross-linking enzyme that confers supra-molecular structures with extra rigidity and resistance against proteolytic degradation, is expressed in the shoulder regions of human atherosclerotic plaques. It has been proposed that TG2 prevents tearing and promotes plaque repair at these potential weak points, and also promotes ectopic calcification of arteries. TG2 is also expressed within plaques that develop within the brachiocephalic arteries of apolipoprotein E (apoE) deficient mice.


OBJECTIVE
To determine the role that TG2 plays in plaque development and calcification, mice were bred that were doubly deficient in apoE and TG2, and were maintained on a high-fat diet for 6 months.


RESULTS
Lesion size and composition were not significantly altered in the apoE/TG2 double-knockout mice, with the exception of a 9.7% decrease in the proportion of the plaque occupied by lipid (p=0.032). The frequency of buried fibrous caps within brachiocephalic plaques was significantly higher in male than in female mice, but TG2 deficiency had no effect on either gender. The extent of lesion calcification varied markedly between individual mice, but it was not decreased in the apoE/TG2 double-knockout mice.


CONCLUSIONS
These data indicate that, in the apoE knockout mouse model of atherosclerosis, TG2 does not influence plaque composition or calcification. The data further suggest that TG2 does not influence plaque stability or repair in these mice.
Williams
Helen
H
Bristol Heart Institute, University of Bristol, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
Pease
Richard J
RJ
Newell
Laura M
LM
Cordell
Paul A
PA
Graham
Robert M
RM
Kearney
Mark T
MT
Jackson
Christopher L
CL
Grant
Peter J
PJ
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology*; D002114:Calcinosis; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000502:physiology*
D001057:Apolipoproteins E; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins