Abstract 168: Splice Variants of Tissue Factor Determine the Coagulant State of Endothelial Cells and Modulate Vascular Stabilization/Regression

Introduction: Recruitment of pericytes (PC), critical to microvascular maturation, requires deposition of basement membrane proteins such as von Willebrand factor (vWF). Loss of PCs ultimately leads to vessel regression and rarefaction. Hypothesis: Splice variants of tissue factor (TF) stabilize the vasculature by supporting EC-PC interactions. Results: We determined that alternatively spliced TF (asTF) resides in Weibel Palade bodies (WPB) of ECs. Overexpression of KLF-2 enhanced asTF protein levels in WPBs. In confluent EC monolayers, asTF was deposited into the extracellular matrix (ECM). In assays employing vascular plexus remodelling on 3D-basement membrane and purified recombinant asTF or full-length TF (flTF), only asTF improved EC-PC interactions. At sites of low KLF-2 expression (low or turbulent flow), total TF mRNA was diminished, leading to low asTF expression. However, upon EC activation by TNFα, total TF mRNA levels rapidly increased and TF protein expression shifted from the ECM-deposited a...