Abstract Number: PB1256
Meeting: ISTH 2022 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Blood Cells and Vessel Wall
Background: Factor VII activating protease (FSAP) is a circulating serine protease that is involved in regulating haemostasis and inflammation. FSAP-deficient mice subjected to thromboembolic stroke exhibit a larger infarct volume, which indicates the protective role of FSAP in the stroke. Our recent research showed that exogenous FSAP is protective in stroke. FSAP has been shown to modulate hyaluronic acid-mediated alterations in endothelial permeability. Therefore, we have investigated the influence of FSAP on the regulation of endothelial permeability by other factors.
Aims: To characterize the role of FSAP in vascular permeability.
Methods: Human umbilical vein endothelial cells (HUVEC) and aorta endothelial cells (HAoEC) were seeded into transwells before they were treated with histones, recombinant human thrombin and human VEGF-A165. The passage of streptavidin-horseradish peroxidase (HRP) through the endothelial monolayer was measured. Immunofluorescence staining of VE-Cadherin and ZO-1 was used to determine the patency of the endothelial layer. Taqman was used to detect the mRNA expression of TLR2. The serine protease domain (SPD) of FSAP was compared to the inactive Marburg-I of FSAP (MI-FSAP).
Results: Histones, thrombin and VEGF significantly increased permeability of HUVEC as well as HAoEC. FSAP-SPD abolished the permeability increases by extracellular histones, but not by thrombin and VEGF. FSAP-SPD alone had no effect on the endothelial permeability. The disturbance of endothelial junctions by the extracellular histones were reversed by FSAP-SPD. FSAP-SPD repressed the overexpression of TLR2 induced by extracellular histones. Inactive MI-FSAP had no such effect.
Conclusion(s): Tissue injury, inflammation and NETosis leads to the release of extracellular histones. Histones activate Pro-FSAP and this, in turn, degrades histones and reverses the increased endothelial permeability by histones. This could contribute to the protective effects of FSAP observed in stroke.
To cite this abstract in AMA style:
Cui X, Stavik B, Sandset P, Kanse S. The role of FSAP in regulating endothelial permeability [abstract]. https://abstracts.isth.org/abstract/the-role-of-fsap-in-regulating-endothelial-permeability/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-role-of-fsap-in-regulating-endothelial-permeability/