This Article Full Text Full Text (PDF) All Versions of this Article: 26/10/2401    most recent 01.ATV.0000240519.46754.9cv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Egorina, E. M. Articles by Østerud, B. Search for Related Content PubMed PubMed Citation Articles by Egorina, E. M. Articles by Østerud, B. Related Collections Animal models of human disease Thrombin Aneurysm, AVM, hematoma

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2401.)
© 2006 American Heart Association, Inc.

Thrombosis

Induction of Monocytic Tissue Factor Expression After Rewarming From Hypothermia In Vivo Is Counteracted by Heat Shock in c-Jun–Dependent Manner

Elena M. Egorina; Mikhail A. Sovershaev; Timofei V. Kondratiev; Jan O. Olsen; Torkjel Tveita; Bjarne Østerud

From the Department of Biochemistry (E.M.E., M.A.S., J.O.O., B.Ø.), Institute of Medical Biology, and the Department of Anesthesiology (T.V.K., T.T.), Institute of Clinical Medicine, University of Tromsø, Norway.

Correspondence to Elena M. Egorina, MD, Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037, Tromsø, Norway. E-mail egorina{at}fagmed.uit.no

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°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-B 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.

In this study we report post-rewarming c-Jun–dependent induction and surface redistribution of active tissue factor antigen in rat mononuclear cells using in vivo model. This induction was counteracted by heat shock pretreatment via upregulation of heat shock protein 70 and suppression of c-Jun activation.

Key Words: heat shock proteins • hypothermia/rewarming • monocytes • rat • tissue factor