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    Oral Communication

    Immunothrombosis

    Mechanisms of Thromboinflammation

    OC 47.4 - The spectrum of light exposure modulates platelet function

    Monday, June 26, 2023
    15:30 – 15:45 ET
    Room: 524
    Session Available As: On-Demand
    Background: Variations in light exposure are associated with changes in inflammation and coagulation. The risk of thrombotic events such as venous thrombosis (VT) and stroke have been found to oscillate with the day-light cycle.

    Aims: To investigate the impact of altering light spectrum on platelet function in thrombosis.

    Methods: WT C57BL/6J mice were exposed to ambient (mice-white, 300lux) or red light (mice-red, 617nm, 1,700lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation and activation were measured. Platelets were isolated and evaluated for transcriptomic and metabolomic changes. The ability of released products of platelet activation to induce thrombosis-generating NET formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. Hemostasis was measured with tail bleeding assays and coagulation biomarkers.

    Results: Exposure to long wavelength red light resulted in reduced platelet aggregation (mice-red 16.0±4.1 vs. mice-white 23.8±5.6 Ohm, p=.02) and activation (P-selectin; mice-red 35.2% vs. mice-white 53.2%; p=.02; Figure 1a). Even though platelet function was reduced, hemostasis assays were not significantly different between groups when mice were exposed to different wavelengths of light. RNA-seq analysis demonstrated no significant transcriptomic changes between mice-red and mice-white. However, there were global metabolomic changes in platelets from mice-red compared to mice-white (Figure 1b). Releasate from activated platelets resulted in reduced NET formation (fold increase from control: mice-red 1.1 vs. mice-white 1.9, p=.03). Mice-red also had reduced VT weight (mice-red 4.2±5.1 mg vs. mice-white 16.5±7.7 mg; p<.01, Figure 2a) and brain infarct size following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p<.01, Figure 2b).

    Conclusion(s): Exposure to long wavelength red light results in reduced platelet aggregation and activation, the reduced capacity to for platelet-dependent NET formation and reduced venous and arterial thrombus burden. Light exposure modulation is a promising alternative for prophylaxis and treatment of venous and arterial thrombosis.

    Learning Objectives:

    • Describe the effects of long wavelength light on thrombosis.
    • Demonstrate the effects of light on platelets in venous thrombosis
    • Demonstrate the effects of light on platelets in arterial thrombosis