Increased tissue transglutaminase expression in human atherosclerotic coronary arteries
Increased tissue transglutaminase expression in human atherosclerotic coronary arteries
复制标题
DOI：
10.1097/mca.0b013e3283108fc3
复制
发表时间：
2008-11-01
影响因子：
1.8
通讯作者：
Kim, Dae-Joong
中科院分区：
文献类型：
--
作者：
Cho, Byung-Ryul;Kim, Min-Kyung;Kim, Dae-Joong
背景和目的转谷氨酰胺酶2 （TGase 2）是一种钙依赖性交联酶，可催化两个蛋白质之间的共价异肽键。有趣的是，这种催化可以通过NF-kappa B抑制蛋白（I-kappa B）的聚合激活核因子-kappa B （NF-kappa B）。本研究的目的是研究TGase 2在人动脉粥样硬化的人冠状动脉中的表达，以及TGase 2在nf - κ B激活中的可能作用。方法与结果探讨TGase 2和NF-kappa B的表达是否与动脉粥样硬化相关。在人类样本中，我们发现随着动脉粥样硬化的进展，冠状动脉粥样硬化的新内膜组织中TGase 2明显高于正常水平。在动脉粥样硬化血管壁中，TGase 2的活性也增加了大约两倍。在免疫荧光分析中，NF-kappa B、COX-2和tnf - α在TGase 2阳性的新内膜平滑肌细胞中共定位。启动子实验表明，tgf - 2介导的NF-kappa B在单核细胞和乳腺癌细胞中的活性均增加，tgf - 2介导的NF-kappa B活化可被tgf - 2 siRNA逆转。结论TGase 2可能在NF-kappa B通路中起激活作用；这种作用可能发生在动脉粥样硬化的血管壁。冠状动脉疾病19:45 59-468 (C) 2008 Wolters Kluwer Health垂直bar Lippincott Williams & Wilkins。
Background and objective Transglutaminase 2 (TGase 2) is a calcium-dependent cross-linking enzyme that catalyzes a covalent iso-peptide bond between two proteins. Interestingly, this catalysis can activate the nuclear factor-kappa B (NF-kappa B) through the polymerization of the inhibitory protein of NF-kappa B (I-kappa B). The objective of the present study was to investigate the expression of TGase 2 in the human atherosclerotic human coronary artery, and the possible roles of TGase 2 in NF-kappa B activation.Methods and results We explored whether expressions of TGase 2 and NF-kappa B are associated in atherosclerosis. Using human samples, we found that TGase 2 was markedly higher than normal in the neointimal tissue of atherosclerotic coronary arteries with atherosclerosis progression. TGase 2 activity was also increased approximately two-fold in the atherosclerotic vascular wall. In immunofluorescence analysis, NF-kappa B, COX-2, and TNF-alpha were co-localized at TGase 2-positive neointimal smooth muscle cells. A promoter assay test showed that NF-kappa B activity increased in both the human monocyte and human breast carcinoma cell by TGase 2, and that TGase 2-mediated NF-kappa B activation was reversed by TGase 2 siRNA.Conclusion According to these results, we suggest that TGase 2 may function as an activator in the NF-kappa B pathway; this effect may occur in the atherosclerotic vessel wall. Coron Artery Dis 19:459-468 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.