TY - JOUR T1 - Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability JF - bioRxiv DO - 10.1101/646109 SP - 646109 AU - Xiaopeng Tang AU - Mingqian Fang AU - Ruomei Cheng AU - Zhiye Zhang AU - Yuming Wang AU - Chuanbin Shen AU - Yajun Han AU - Qiumin Lu AU - Yingrong Du AU - Yingying Liu AU - Zhaohui Sun AU - Liping Zhu AU - James Mwangi AU - Min Xue AU - Chengbo Long AU - Ren Lai Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/04/646109.abstract N2 - In the accompanying manuscript, transferrin has been demonstrated to maintain coagulation balance by interacting with clotting factors, suggesting that elevated transferrin causes thromboembolic diseases and factors up-regulating transferrin is associated with thrombosis. Here we show that transferrin and transferrin-thrombin/FXIIa complexes are elevated in plasma and cerebrospinal fluid of ischemic stroke (IS) patients with iron-deficiency anemia (IDA) history, IDA patients and venous thromboembolism patients using combined oral contraceptives (CC) as well as ID mice, suggesting an association of transferrin up-regulation with ID and CC. ID and estrogen up-regulated transferrin through hypoxia and estrogen response elements located at transferrin gene enhancer and promoter region, respectively. ID, exogenous transferrin/estrogen administration or transferrin over-expression promoted hypercoagulability and aggravated IS, while anti-transferrin antibody, transferrin knockdown or designed peptide inhibitors interfering transferrin-thrombin/FXIIa interaction exerted anti-IS effects in vivo. Collectively, the results reveal that factors (i.e., ID and CC) up-regulating transferrin are risk factors of thromboembolic diseases. ER -