Abstract 27: Galectin-3 Binding Protein: A New Factor Promoting Venous Thrombosis

Abstract

Galectin-3 binding protein (Gal-3BP) was detected in procoagulant microparticles from mice and patients with venous thrombosis (VT), in prior studies from our laboratory. However, the mechanistic role of Gal-3BP and Galactin-3 (Gal-3) in the pathophysiology of thrombosis is unknown. Our hypothesis is that Gal-3BP and Gal-3 are critical to thrombus formation. Methods: Mice : Using our inferior vena cava ligation mouse model of VT, microparticle samples from thrombosed and non-thrombosed wild type mice were analyzed for Gal-3BP. We then either neutralized Gal-3BP, using an antibody (Anti-M-Gal-3BP), or utilized Gal-3 knock-out (Gal-3 KO) mice, compared to mice given saline as controls (NaCl). We evaluated thrombus weight (TW), inflammatory cell counts, and the cell source of the molecules Gal-3BP and Gal-3 using western blot. Patients: Microparticles and plasma samples from patients who were positive or negative for VT were tested for Gal-3BP using ELISA. Results: Mice : Two days after thrombosis, blocking Gal-3BP significantly reduced both vein wall inflammatory cells ( p =0.0369) and TW ( p =0.0024), compared to NaCl. In Gal-3 KO mice, TW was significantly smaller versus controls ( p =0.0061). We found Gal-3BP on microparticles and platelets while Gal-3 was on monocytes. Patients : Gal-3BP was significantly elevated in microparticles ( p =0.0495) and in plasma ( p =0.0400), versus patients negative for VT. Conclusions: We demonstrated a clear link between Gal-3BP and VT, in both mice and patients. This is the first time that Gal-3BP has been shown to be involved with thrombus formation, making it a promising biomarker and potential target for therapeutic interventions of VT.