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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Atherosclerotic plaque caps are locally weakened when macrophages density is increased.Atherosclerosis. 1991; 87: 87-90
- Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma; a potential mechanism of lesion stabilization.Circulation. 1998; 97: 2433-2444
- Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues.FASEB J. 1991; 5: 3071-3077
- Detection of epsilon (gamma-glutamyl) lysine.Mol. Cell. Biochem. 1984; 58: 37-49
- Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells.Mol. Cell. Biol. 1994; 14: 6584-6596
- Differential expression of tissue transglutaminase in human cells. An immunohistochemical study.Cell. Tissue Res. 1989; 255: 215-224
- The transglutaminase in vascular cells and tissues could provide an alternate pathway for fibrin stabilization.Blood. 1987; 70: 702-709
- Increased transglutaminase in the aortas of cholesterol-fed rabbits: occurrence of buffer soluble and insoluble forms and an inhibitor.Biochem. Cell. Biol. 1991; 69: 821-827
- Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence.J. Biol. Chem. 1990; 265: 14791-14795
- The trappin gene family: proteins defined by an N-terminal transglutaminase substrate domain and a C-terminal four-disulphide core.Biochem. J. 1999; 340: 569-577
- Endothelial constitutive nitric oxide synthase protein and mRNA increased in rabbit atherosclerotic aorta despite impaired endothelium-dependent vascular relaxation.Am. J. Pathol. 1996; 148: 1949-1956
- Expression of NADH/NADPH oxidase p22phox in human coronary arteries.Circulation. 1999; 100: 1494-1498
- Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells.J. Biol. Chem. 1993; 268: 24959-24966
- Angiotensin II inhibits cytokine-stimulated inducible nitric oxide synthase expression in vascular smooth muscle cells.J. Biol. Chem. 1994; 269: 11628-11633
- Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen.J. Biol. Chem. 1987; 262: 1022-1024
- TNF-α modulates expression of the tissue transglutaminase gene in liver cells.Am. J. Physiol. 1998; 274: G240-G245
- Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-α.Circulation. 1996; 94: 2787-2792
- The ε-(γ-glutamyl) lysine crosslink and the catalytic role of transglutaminases.Adv. Protein Chem. 1977; 31: 1-133
- Tissue transglutaminase; an enzyme with a split personality.Int. J. Biochem. Cell. Biol. 1999; 31: 817-836
- A novel guanitine nucleotide-binding protein coupled to the α1-adrenergic receptor.J. Biol. Chem. 1990; 65: 944-951
- TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent.Hypertension. 1999; 33: 183-189
- Human monocytes/macrophages release TNF-alpha in response to Ox-LDL.Arterioscler. Thromb. Vasc. Biol. 1996; 16: 1573-1579
- Tumor necrosis factor-alpha activates smooth muscle cell migration in culture and is expressed in the balloon-injured rat aorta.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 490-497
- Isolation and characterization of the human tissue transglutaminase gene promoter.J. Biol. Chem. 1995; 270: 9748-9756
- Tumour necrosis factor alpha activates a p22phox-based NADH oxidase in vascular smooth muscle.Biochem. J. 1998; 329: 653-657
- Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-alpha-induced oxidant stress.Am. J. Physiol. 1999; 276: L979-L988
- An intronic NF-kappaB element is essential for induction of the human manganese superoxide dismutase gene by tumor necrosis factor-alpha and interleukin-1beta.DNA Cell Biol. 1999; 18: 709-722
- Physical and functional sensitivity of zinc finger transcription factors to redox change.Mol. Cell. Biol. 1996; 16: 1035-1046
4S Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S), Lancet 1994; 344: 1383–1389.
- Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease.Circulation. 1993; 87: 1781-1791
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.
