Transferrin plays a central role in coagulation balance by interacting with clotting factors

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2020,（2）
• 页码范围: 119-132
• 页数: 14页
• 语种: 英文

摘要

Coagulation balance is maintained through fine-tuned interactions among dotting 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 Xlla (FXlla),and AT with different affinity to maintain coagulation balance.Normally,transferrin is 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/FXlla 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 transferrin inhibition via shRNA knockdown or treatment with antitransferrin antibody or designed peptides interfering with transferrin-thrombin/FXlla 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.