EXPRESSION OF THIOREDOXIN IS ENHANCED IN ATHEROSCLEROTIC PLAQUES AND DURING NEOINTIMA FORMATION IN RAT ARTERIES

Thioredoxin (TRX) is an intracellular enzyme that has a variety of act ivities as a hydrogen donor for various intracellular molecules. In th e present study, we investigated the role of TRX in atherosclerotic le sions. In human atherosclerotic specimens, TRX and TRX mRNA were enhan ced in endothelial cells and macrophages in the atherosclerotic plaque s. In balloon-injured rat arteries, TRX expression increased from 2 to 6 weeks after injury; TRX was induced in the neointimal regenerating endothelial cells. In hybridization experiments, TRX mRNA was also ind uced from 2 to 6 weeks in the endothelium. in this model, inducible ni tric oxide synthase immunoreactivity in the neointimal smooth muscle c ells and endothelial cells increased from 2 to 6 weeks after surgical procedures were performed. During this period, the immunoreactivity of nitrotyrosine, which is a marker of nitric oxide (NO) production, als o increased. We focused on the association between TRX and NO. In vitr o studies using a murine endothelial cell line showed TRX and TRX mRNA induction by NO and peroxynitrite donors. Enhanced expression of TRX was detected mainly within the cytoplasm in immunocytochemical studies . In addition, TRX-transfected cells showed resistance to peroxynitrit e-induced cytotoxicity. These findings indicate that TRX and the cellu lar redox state modified by TRX play a crucial role in arterial neoint ima formation in atherosclerosis.