Localization of Tissue Transglutaminase in Human Carotid and Coronary Artery Atherosclerosis: Implications for Plaque Stability and Progression
| Autor: | Reidar Wallin, Madhu Gupta, Charles S. Greenberg, Thomas Wannenburg, David C. Sane, Zishan A. Haroon |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Carotid Artery Diseases Male Pathology medicine.medical_specialty Tissue transglutaminase Coronary Artery Disease Matrix metalloproteinase Pathology and Forensic Medicine medicine Humans Molecular Biology Aged Aged 80 and over Transglutaminases biology Vascular disease business.industry Coronary artery atherosclerosis Cell Biology Middle Aged medicine.disease Immunohistochemistry Coronary heart disease Pathophysiology biology.protein Female business |
| Zdroj: | Laboratory Investigation. 81:83-93 |
| ISSN: | 0023-6837 |
| Popis: | Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of epsilon(gamma-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product epsilon(gamma-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components. |
| Databáze: | OpenAIRE |
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