RT Journal Article
SR Electronic
T1 Transferrin plays a central role to maintain coagulation balance by interacting with clotting factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 646075
DO 10.1101/646075
A1 Tang, Xiaopeng
A1 Zhang, Zhiye
A1 Fang, Mingqian
A1 Han, Yajun
A1 Wang, Sheng
A1 Xue, Min
A1 Li, Yaxiong
A1 Zhang, Li
A1 Wu, Jian
A1 Yang, Biqing
A1 Lu, Qiumin
A1 Du, Xiaoping
A1 Lai, Ren
YR 2019
UL http://biorxiv.org/content/early/2019/07/05/646075.abstract
AB Coagulation balance is maintained through fine-tuning interactions among clotting factors. Physiological concentrations of clotting factors are huge difference. Especially, coagulation proteases’ concentration (pM to nM) is much lower than their natural inactivator antithrombin III (AT-III, ∼3 μM). Here we show that transferrin (normal plasma concentration ∼40 μM) interacts with fibrinogen, thrombin, FXIIa and AT-III with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration ∼10 μM) with a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT-III’s inactivation on coagulation proteases by binding to AT-III, and thus induces hypercoagulability. In mouse models, transferrin-overexpression aggravated atherosclerosis while transferrin-knockdown, anti-transferrin antibody or designed peptides interfering transferrin-thrombin/FXIIa interactions alleviated it. Collectively, these findings identify transferrin as a clotting factor and an adjuster for maintaining coagulation balance and modify the coagulation cascade.