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 activities as a hydrogen donor for various intracellular molecules. In the present study, we investigated the role of TRX in atherosclerotic lesions. In human atherosclerotic specimens, TRX and TRX mRNA were enhanced in endothelial cells and macrophages in the atherosclerotic plaques. 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 induced from 2 to 6 weeks in the endothelium. In this model, inducible nitric oxide synthase immunoreactivity in the neointimal smooth muscle cells 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, also increased. We focused on the association between TRX and NO. In vitro 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 peroxynitrite-induced cytotoxicity. These findings indicate that TRX and the cellular redox state modified by TRX play a crucial role in arterial neointima formation in atherosclerosis.
Department of Neurosurgery, Faculty of Medicine, Kyoto University, Sakyo, Japan.
Y
Y
Takagi
Y
Y
Gon
T
T
Todaka
K
K
Nozaki
A
A
Nishiyama
H
H
Sono
N
N
Hashimoto
H
H
Kikuchi
J
J
Yodoi
D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009566:Nitrates / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D016877:Oxidants / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D017539:Tunica Intima / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000096:biosynthesis
D009566:Nitrates; D016877:Oxidants; D012333:RNA, Messenger; C039642:peroxynitric acid; D009569:Nitric Oxide; D014443:Tyrosine; D013879:Thioredoxins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat