Expression of glutaredoxin in human coronary arteries - Its potential role in antioxidant protection against atherosclerosis
Expression of glutaredoxin in human coronary arteries - Its potential role in antioxidant protection against atherosclerosis
复制标题
DOI：
10.1161/hq0901.095550
复制
发表时间：
2001-09-01
影响因子：
8.7
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
--
作者：
Okuda, M;Inoue, N;Yokoyama, M
氧化应激被认为是动脉粥样硬化发生的重要因素。哺乳动物细胞具有复杂的抗氧化剂网络，如过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶。然而，调控血管壁细胞氧化还原状态的机制尚不清楚。最近的研究表明，硫氧还蛋白是一种硫醇二硫氧化还原酶，在人颈动脉粥样硬化斑块中表达。在这项研究中，我们研究了戊二氧还蛋白（glutaredoxin）和硫氧还蛋白（thioredoxin）这两个重要成员在人冠状动脉解剖样本中的定位和表达变化。在非动脉粥样硬化的冠状动脉中，glutaredoxin在内皮细胞、外膜成纤维细胞中表达，在内侧平滑肌细胞中表达最强烈。有趣的是，在动脉粥样硬化病变如高细胞病变中，浸润的巨噬细胞高度表达glutaredoxin。硫氧还蛋白的表达模式与戊氧还蛋白非常相似。Western blot分析表明，过氧化氢刺激培养的人冠状动脉平滑肌细胞中glutaredoxin的表达呈时间和剂量依赖性。荧光微形貌分析表明，活性氧的产生与glutaredoxin的表达有关。这些结果提示巯基二硫氧化还原酶可能参与人冠状动脉的抗氧化保护。
Oxidative stress is considered an important factor in atherogenesis. Mammalian cells have a complex network of antioxidants such as catalase, superoxide dismutase, and glutathione peroxidase. However, the mechanisms that regulate the cellular redox state in the vessel wall remain unclear. Recent study has shown that thioredoxin, a thiol-disulfide oxidoreductase, is expressed in atherosclerotic plaques of human carotid arteries. In this study, we investigated the localization and expressional change of glutaredoxin and thioredoxin, two important members of the thiol-disulfide oxidoreductases, in autopsy samples of human coronary arteries. In nonatherosclerotic coronary arteries, glutaredoxin was expressed in endothelial cells, in fibroblasts of the adventitia, and most intensely in medial smooth muscle cells. Interestingly, in atherosclerotic lesions such as hypercellular lesions, the infiltrating macrophages highly expressed glutaredoxin. The expressional pattern of thioredoxin was quite similar to that of glutaredoxin. Western blot analysis demonstrated that hydrogen peroxide stimulated the expression of glutaredoxin in a time- and dose-dependent manner in cultured human coronary artery smooth muscle cells. Fluorescence microtopography with dihydroethidium demonstrated that the generation of reactive oxygen species was associated with the expression of glutaredoxin. These results suggest the possible involvement of thiol-disulfide oxidoreductases in antioxidant protection in human coronary arteries.