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 Xiaopeng Tang
A1 Zhiye Zhang
A1 Mingqian Fang
A1 Yajun Han
A1 Sheng Wang
A1 Min Xue
A1 Yaxiong Li
A1 Li Zhang
A1 Jian Wu
A1 Biqing Yang
A1 Qiumin Lu
A1 Xiaoping Du
A1 Ren Lai
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.