Abstract 24: Resolvin D2 Reduces Thrombus Burden and Attenuates Inflammatory Signaling Pathways in a Murine Model of Venous Thrombosis

Abstract

Background: Specialized pro-resolving lipid mediators (SPM) derived from polyunsaturated fatty acids, such as Resolvin D2 (RvD2), play a critical role in the resolution of acute inflammation. In recent years, total organic synthesis of SPM have enabled investigation of their bioactivity in-vivo. It is known that the effects of RvD2 include limited neutrophil influx in-vivo, reduced neutrophil transmigration and counter-regulation of cytokines such as tumor necrosis factor-α TNF-α in mice. However, SPMs have not been studied in the context of experimental venous thrombosis (VT). Methods: Mice C57Bl/6, 10 week-old, 25grams. Groups: Control non-VT mice; VT-control-vehicle; VT-RvD2; Flow model: Electrolytic IVC model. Intra-peritoneal injection was used for RvD2 and vehicle administration 4 hours after surgery. Harvest was performed 2 days after surgery, acute VT. Thrombus weight, qRT-PCR for inflammatory cytokines panel and subsets of white blood cell (WBC) counts were performed at the site of thrombosis histologically. Results (Figure 1): We observed that RvD2 significantly reduced thrombus size when compared to vehicle controls (17.9mg±2.1mg vs. 4.5mg±0.8mg). The vein wall cytokine profile demonstrated a significant gene down-regulation of IL-6, CCL2, and TNF-a. In addition, the inflammatory cell counts showed reduction in all white cells subsets. No bleeding complications were observed. Conclusions: For the first time we have demonstrated that RvD2 reduces VT formation. The decreased thrombogenesis was accompanied by a decrease in WBC and proinflammatory cytokines. We demonstrated that RvD2 is a potent anti-inflammatory agent that reduced WBC and attenuated cytokines in the context of experimental VT. Further investigation of RvD2 in VT treatment and prophylaxis appears warranted.