Abstract:
von Willebrand factor (vWF) is a large plasma glycoprotein that plays an important role in hemostasis by
forming molecular bridges with platelets following vascular injury. Previously, we reported that hypothermia
enhanced vWF production in the spleen, which resulted in the activation of the platelet pool in a
hypothermia-induced murine model. However, the mechanisms that regulate vWF expression under
hypothermic conditions remain unclear. In this study, we focused on vWF expression under hypothermic
conditions in splenic endothelial cell culture.
Human splenic endothelial cells (HSEC) were incubated at 20 C for 1 h. Total RNA was extracted from
the cells, and cDNA microarray gene expression analysis was performed. Genes that may be associated
with vWF expression in low temperature culture conditions were then selected for further analysis.
Gene expression analysis showed that low temperature conditions increased the expression of FOS
and EGR1. We then hypothesized that these factors upregulate vWF mRNA expression in HSEC. The
transcriptional inhibitors of EGR1 significantly inhibited vWF mRNA expression in HSEC cultured at a low
temperature.
Our analysis revealed that low temperatures enhance the gene expression of EGR1, which transcriptionally
increases vWF expression. This acute-phase reaction may play an important role in platelet
activation in the spleen during hypothermia.