title: Expression of tissue transglutaminase and elafin in human coronary artery: implication for plaque instability.
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).
  
  
  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-alpha, suggesting that this cytokine might play an important role in the regulation of tTG. Treatment of cultured rat aortic SMCs with TNF-alpha 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-alpha 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.
authors.affiliation: First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sumi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azumi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Seno
authors.forename: Masanori
authors.initials: M
authors.lastname: Okuda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001344:Autopsy; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D011503:Transglutaminases / Q000096:biosynthesis* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011503:Transglutaminases