| 论文题目: | Transferrin Plays a Central Role in Coagulation Balance by Interacting with Clotting Factors |
| 作者: | Tang X, Zhang Z, Fang M, Han Y, Wang G, Wang S, Xue M, Li Y, Zhang L, Wu J, Yang B, Mwangi J, Lu Q, Du X, Lai R |
| 联系作者: | rlai@mail.kiz.ac.cn |
| 发表年度: | 2019 |
| DOI: | doi: 10.1038/s41422-019-0260-6 |
| 摘要: | Coagulation balance is maintained through fine-tuned interactions among clotting factors, whose physiological concentrations vary substantially. In particular, the concentrations of coagulation proteases (pM to nM) are much lower than their natural inactivator antithrombin (AT,？~？3？μM), suggesting the existence of other coordinators. In the current study, we found that transferrin (normal plasma concentration？~40？μM) interacts with fibrinogen, thrombin, factor XIIa (FXIIa), and AT with different affinity to maintain coagulation balance. Normally, transferrinis sequestered by binding with fibrinogen (normal plasma concentration？~10？μM) at a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT's inactivation effect on coagulation proteases by binding to AT, thus inducing hypercoagulability. In the mouse model, transferrin overexpression aggravated atherosclerosis, whereas transferrininhibition via shRNA knockdown or treatment with anti-transferrin antibody or designed peptides interfering with transferrin-thrombin/FXIIa interactions alleviated atherosclerosis. Collectively, these findings identify that transferrin is an important clotting regulator and an adjuster in the maintenance of coagulation balance and modifies the coagulation cascade |
| 刊物名称: | Cell Research |
| 论文出处: | https://www.nature.com/articles/s41422-019-0260-6 |
| 影响因子: | 17.848(2018年) |
