Association of Organ Preservation Methods With Von Willebrand Factor Upregulation in Microvascular Endothelial Cells Posttransplantation: Ex Vivo Lung Perfusion and Static Cold Storage.

BACKGROUND: Von Willebrand factor (VWF) is a procoagulant glycoprotein expressed exclusively in endothelial cells and megakaryocytes. It mediates platelet adhesion to endothelial/subendothelial surfaces and initiates thrombogenesis. External stimuli, including hypoxia, were shown to upregulate VWF expression levels and alter its vascular tree expression pattern in the lung. Increased VWF levels are a significant risk factor for thrombus formation, a major complication in organ transplantation. Given that donor organs experience hypoxic conditions during transplantation, this study investigates whether hypoxia alters VWF expression and whether modifying organ preservation to reduce hypoxic exposure could prevent these alterations.

METHODS: Porcine procured lungs were maintained in either static cold storage (SCS) or ex vivo lung perfusion with warm perfusion. Lung tissue biopsies were obtained immediately after organ procurement, 12 h post-cold storage, or post-warm perfusion. VWF RNA and protein expression levels and patterns were analyzed using reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence.

RESULTS: Immunofluorescent analysis demonstrated that transplanted lungs maintained under SCS, but not ex vivo lung perfusion, exhibited VWF expression in an increasing number of microvascular endothelial cells, whereas warm perfusion led to a significant reduction in VWF mRNA levels, and it also showed a clear trend toward reduced protein expression compared with cold storage.

CONCLUSIONS: Increased VWF expression in microvascular endothelial cells under SCS may contribute to transplant-associated thrombogenicity. Decreasing VWF expression through ex vivo normothermic perfusion could significantly mitigate the risk of thrombogenic complications, a major complication of organ transplantation.