Details

Autor(en) / Beteiligte

• Awad, E. M.
• Khan, S. Y.
• Sokolikova, B.
• Brunner, P. M.
• Olcaydu, D.
• Wojta, J.
• Breuss, J. M.
• Uhrin, P.

Titel

Cold induces reactive oxygen species production and activation of the NF‐kappa B response in endothelial cells and inflammation in vivo

Ist Teil von

• Journal of thrombosis and haemostasis, 2013-09, Vol.11 (9), p.1716-1726

Ort / Verlag

England: Elsevier Limited

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Background Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ. Objectives In this study we analyzed cold‐induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure. Methods We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37 °C (mostly to 8 °C) for 30 min and upon rewarming to 37 °C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold. Results The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor‐1 (PAI‐1) and tissue factor (TF) and of the inflammatory adhesion molecules, E‐selectin, intracellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF‐κB pathway, as measured by transient NF‐κB translocation to the nucleus and IκBα degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold‐induced NF‐κB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM‐1 expression and resulted in leukocyte infiltration. Conclusions Our results point to a causative link between ROS production and NF‐κB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation.