Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude

	Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude
	Li, MQ; Tang, XP; Liao, ZY; Shen, CB; Cheng, RM; Fang, MQ; Wang, G; Li, Y; Tang, SZ; Xie, L; Zhang, ZY; Kamau, PM; Mwangi, J; Lu, QM; Li, YX; Wang, YM; MacKeigan, DT; Cerenzia, EG; Ni, HY; Lai, R
	2022
发表期刊	BLOOD
ISSN	0006-4971
卷号	140 期号:19 页码:2063-2075
摘要	Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes. We found that the activities of thrombin and factor XIIa (FXIIa) along with the concentrations of transferrin were significantly increased in the plasma of humans and mice at high altitudes. Furthermore, both hypoxia (6% O-2) and low temperature (0 degrees C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1 alpha (HIF-1 alpha) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1 alpha binding site, and consequently, to induce hypercoagulability by potentiating thrombin and FXIIa. Importantly, thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature were ameliorated by transferrin interferences, including transferrin antibody treatment, transferrin down - regulation, and the administration of our designed peptides that inhibit the potentiation of transferrin on thrombin and FXIIa. Thus, low temperature and hypoxia upregulated transferrin expression-promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and potentially powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13252
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Li, MQ,Tang, XP,Liao, ZY,et al. Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude[J]. BLOOD,2022,140(19):2063-2075.
APA	Li, MQ.,Tang, XP.,Liao, ZY.,Shen, CB.,Cheng, RM.,...&Lai, R.(2022).Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude.BLOOD,140(19),2063-2075.
MLA	Li, MQ,et al."Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude".BLOOD 140.19(2022):2063-2075.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023032154.pdf（3783KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文