PT  - JOURNAL ARTICLE
AU  - Tang, Xiaopeng
AU  - Zhang, Zhiye
AU  - Fang, Mingqian
AU  - Han, Yajun
AU  - Wang, Sheng
AU  - Xue, Min
AU  - Li, Yaxiong
AU  - Zhang, Li
AU  - Wu, Jian
AU  - Yang, Biqing
AU  - Lu, Qiumin
AU  - Du, Xiaoping
AU  - Lai, Ren
TI  - Transferrin plays a central role to maintain coagulation balance by interacting with clotting factors
AID  - 10.1101/646075
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 646075
4099  - http://biorxiv.org/content/early/2019/07/05/646075.short
4100  - http://biorxiv.org/content/early/2019/07/05/646075.full
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.