Abstract
Background: the extracellular matrix (ECM) is an important determinant of plaque instability.
Since tissue transglutaminase (tTG) and elafin act as stabilizing factors, they might
play a crucial role in the pathogenesis of acute coronary syndrome. We examined their
expression in human coronary arteries and the regulation of tTG expression in cultured
vascular smooth muscle cells (SMCs). Methods and results: immunohistochemical studies on autopsy samples of human coronary arteries revealed
the expression of tTG and elafin in the endothelium, medial SMCs, and the ECM in non-atherosclerotic
coronary arteries. Their expression in SMCs, endothelium, and ECM was enhanced in
atherosclerotic coronary arteries. In contrast, they were hardly detectable in accumulating
macrophages or at the lipid core. Double staining demonstrated that elafin was co-localized
with tTG. Moreover, some tTG-expressing cells were positive for TNF-α, suggesting
that this cytokine might play an important role in the regulation of tTG. Treatment
of cultured rat aortic SMCs with TNF-α increased their tTG mRNA, protein expression
and enzyme activity. Conclusions: the expression of tTG and elafin increased in atherosclerotic coronary arteries.
The investigation with cultured SMCs suggested that TNF-α might mediate the upregulation
of tTG. Our findings may provide new insights into the mechanism of plaque instability
and the pathogenesis of acute coronary syndrome.
Keywords
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Article info
Publication history
Accepted:
April 30,
2001
Received:
October 5,
2000
Identification
Copyright
© 2002 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.