Expression of tissue transglutaminase and elafin in human coronary artery: Implication for plaque instability

• Published in: Atherosclerosis 2002, Vol.160 (1), p.31-39
• Main Authors: Sumi, Yoshihiko, Inoue, Nobutaka, Azumi, Hiroshi, Seno, Tadashi, Okuda, Masanori, Hirata, Ken-ichi, Kawashima, Seinosuke, Hayashi, Yoshitake, Itoh, Hiroshi, Yokoyama, Mitsuhiro
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Autopsy; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary Artery Disease - metabolism; Coronary Vessels - drug effects; Coronary Vessels - enzymology; Dose-Response Relationship, Drug; Elafin; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Humans; Immunohistochemistry; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Protein Biosynthesis; Proteinase Inhibitory Proteins, Secretory; Proteins - drug effects; Rats; RNA, Messenger - biosynthesis; RNA, Messenger - drug effects; Time Factors; Transglutaminase; Transglutaminases - biosynthesis; Transglutaminases - drug effects; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation - drug effects
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(01)00542-1

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.