Abstract Number: PB0892
Meeting: ISTH 2022 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: PCSK9 is a serine protease that induces endosomal and lysosomal degradation of the LDL receptor, which leads to increased plasma LDL-cholesterol levels. Recent studies have shown that PCSK9 is involved in the pathophysiology of inflammation and has effects on other cell types.
Aims: Aim of the present study was to investigate the effect of mature recombinant PCSK9 (recPCSK9) on platelet aggregation and on the expression of inflammatory markers on endothelial cells.
Methods: Washed platelets (WP) were isolated from healthy volunteers and adjusted at 250.000 platelets/μl. WP were incubated with various concentrations of PCSK9 and then activated with (0.01-0.025 units/ml) thrombin or (0.25mm) Aracidonic Acid (AA) that induces platelet aggregation 20 and 28%, respectively which was monitored by Light Transmittance Aggregometry. Human Umbilical Vein Endothelial Cells (HUVECs) were cultured to reach confluency and then pre-incubated with recPCSK9 for 5min followed by activation with (0.05 ng/ml) Tumor Necrosis Factor-α (TNF-α) for 6h. Cell activation was studied by the determination of the membrane expression of ICAM-1 (Intercellular Adhesion Molecule-1) using flow cytometry and the fluorescently labeled antibody, CD54-PE.
Results: recPCSK9 at concentrations of 300-1600ng/ml does not induce platelet aggregation, however at concentrations ≥800ng/ml it increases by 2.5 times the thrombin-induced platelet aggregation (from 20 to 48%) and doubles the platelet aggregation induced by A.A (from 28 to 56%). recPCSK9 at concentrations of 500-1500 ng/ml does not induce the expression of ICAM-1 in HUVECs (MFI values), while it enhances the action of TNF-α by 1.5 times at a concentration of 1.000 ng/ml (from 53 to 79.5) and by 2.5 times at a concentration of 1.500 ng/ml (from 53 to 132.5).
Conclusion(s): recPCSK9 potentiates the thrombin- or AA-induced platelet activation as well as the inflammatory activation of the endothelial cells. The underlying mechanisms, as well as the significance of this action at the clinical level, are under investigation.
To cite this abstract in AMA style:
Tsouka A, Tselepis A. The effect of PCSK9 on platelet aggregation and on the inflammatory activation of endothelial cells [abstract]. https://abstracts.isth.org/abstract/the-effect-of-pcsk9-on-platelet-aggregation-and-on-the-inflammatory-activation-of-endothelial-cells/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-effect-of-pcsk9-on-platelet-aggregation-and-on-the-inflammatory-activation-of-endothelial-cells/