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  • Title: Induction of monocytic tissue factor expression after rewarming from hypothermia in vivo is counteracted by heat shock in c-Jun-dependent manner.
    Author: Egorina EM, Sovershaev MA, Kondratiev TV, Olsen JO, Tveita T, Østerud B.
    Journal: Arterioscler Thromb Vasc Biol; 2006 Oct; 26(10):2401-6. PubMed ID: 16902157.
    Abstract:
    OBJECTIVE: Triggering of tissue factor (TF)-mediated blood coagulation leads to the development of disseminated intravascular coagulation during rewarming from hypothermia. We studied post-rewarming TF levels, activity, and surface redistribution, along with the regulation of TF gene transcription in mononuclear cells (MNCs) obtained from an in vivo rat model. METHODS AND RESULTS: Rewarming after a 5-hour episode of 15 degrees C hypothermia caused an increase in TF activity, protein levels, and externalization of TF antigen in rat MNCs. This was accompanied by a dramatic elevation of c-Jun and JNK phosphorylation, and the absence of EGR-1 and NF-kappaB activation. To search for a stimulus to counteract c-Jun-mediated induction of TF activity in MNCs from rewarmed rats, we applied heat shock pretreatment one day before the hypothermia/rewarming experiment. This restored post-rewarming TF activity, protein levels, and surface-to-total TF ratio in rat MNCs to normothermic levels. Furthermore, in heat shock-pretreated animals, rewarming failed to increase phosphorylated c-Jun and JNK levels. We attribute this to the profound overexpression of heat shock protein 70 and inhibition of JNK. CONCLUSIONS: MNCs respond to rewarming from hypothermia by an induction of active TF antigen. This effect is dependent on c-Jun activation and is abolished by heat shock pretreatment.
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