HAEMATOLOGY RESEARCH GROUP
The endothelial “side” of thromboinflammation
HIT and VITT are severe thrombotic conditions triggered by autoimmune antibodies directed against a platelet protein, platelet factor 4 (PF4), which assemble on the vascular endothelium. We have found that the endothelium upregulates tissue factor activity in response to HIT and VITT antibodies which drives thromboinflammation. We are investigating the interaction of lymphocytes with the endothelium in HIT and developing novel inhibitors of the HIT and VITT antibody to dampen the immune thrombotic response in these serious conditions.
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A. VITT serum induces endothelial expression of tissue factor which is enhanced with the addition of platelet factor 4. Images of human umbilical endothelial cells (HUVECs) stained for tissue factor (green), after exposure to media, vax control serum, vax control serum + PF4, VITT serum, VITT serum + PF4 and TNF-a. Nuclear staining by Hoechst is shown in blue. B. Fold change in mRNA expression of tissue factor in HUVECs treated with plasma, with or without PF4, compared with media alone.