Blood coagulation and lipoproteins systems take part in regulation of endothelial cell functions. We focus on: 1, the factor V (FV) isoform/ tissue factor pathway inhibitor (TFPIα) anticoagulant mechanism, 2, apoM/sphingosine-1-phosphate (S1P)-containing HDL, and 3, the protein S/Gas6/TAM tyrosine-kinase receptor pathway. A FV isoform and TFPIα are components of a novel anticoagulant mechanism in which an alternatively spliced FV (FV-Short) forms a high affinity interaction with TFPIα. TFPIα is an efficient inhibitor of blood coagulation, present both on endothelium and in circulation.

The second topic involves HDL-associated apoM, which we have studied intensively since we discovered the protein. We found that apoM is the carrier of S1P, which is an important lipid mediator that mediates vascular wall protections through interactions with S1P receptors on endothelial cells.

The third topic focuses on TAM receptors and their vitamin K-dependent protein ligands Gas6 and protein S. Both receptors and ligands are expressed by endothelium, but the physiological role of this receptor-ligand system in endothelium is poorly understood.

We wish to elucidate the physiological mechanisms and importance of the TFPIα/FV isoform anticoagulant pathway, of the apoM/S1P-HDL system, and of the Gas6/protein S/TAM receptor pathway and to clarify how these systems influence endothelial functions. We aim to determine the functional importance of the apoM/S1P complex and clarify the S1P receptor-specificity for apoM/S1P. Moreover, we aim at clarifying the importance of the Gas6/protein S/TAM pathway in regulation of endothelial cell inflammation and the importance of the TAM system for clearance of microparticles by endothelium.