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

Area of Science:

• Biochemistry
• Physiology
• Environmental Medicine

Background:

• High altitude is associated with increased thromboembolic events.
• The precise mechanism linking high altitude to hypercoagulability remains unclear.
• Previous research indicated transferrin's role in potentiating blood coagulation.

Purpose of the Study:

• To investigate the mechanism of high altitude-related thromboembolism.
• To examine the relationship between altitude, transferrin, and coagulation factors.
• To identify potential therapeutic targets for high-altitude thromboembolic disorders.

Main Methods:

• Plasma samples from humans and mice at varying altitudes were analyzed for coagulation factors and transferrin.
• Hypoxia and low temperature effects on hypoxia-inducible factor 1α (HIF-1α) and transferrin gene expression were studied.
• Mouse models were used to test the efficacy of transferrin interference strategies against induced thromboembolism.

Main Results:

• Transferrin concentrations and activities of thrombin and factor XIIa (FXIIa) were elevated at high altitudes in both humans and mice.
• Hypoxia and low temperature increased HIF-1α, promoting transferrin gene expression and hypercoagulability.
• Transferrin interference (antibody, downregulation, peptide inhibitors) ameliorated hypoxia- and cold-induced thromboembolic events in mice.

Conclusions:

• High altitude, through hypoxia and low temperature, upregulates transferrin expression, leading to hypercoagulability.
• The transferrin-coagulation pathway is a key mediator of high altitude-induced thromboembolism.
• Targeting transferrin offers a novel therapeutic strategy for preventing thromboembolic events in high-altitude environments.