Low-Molecular-Weight Fucoidan Inhibits Thromboinflammation and Ameliorates Deep Vein Thrombosis via Targeting S100A8/A9

Deep vein thrombosis (DVT) is a prevalent life-threatening complication among hospitalized patients. DVT is characterized by the hypercoagulability and thromboinflammation in which platelet activation and neutrophil extracellular trap (NET) formation are critically involved. Studies have shown that S100A8/A9 is significantly elevated in patients with DVT, and is closely associated with platelet activation and NET formation. Fucoidan, the marine polysaccharide derived from Fucus algae, has potential anti-inflammatory and cardioprotective effects. We found low-molecular-weight fucoidan (LMF) bound to S100A8/A9 with an equilibrium dissociation constant (KD) of 2.368 × 10^-8 M. LMF inhibited S100A8/A9-induced platelet hyperactivity and NET formation in vitro, and ameliorated DVT without significantly perturbing hemostasis in vivo. Our results indicate that the alarmin protein S100A8/A9 is a novel target of LMF. LMF may have therapeutic potential in S100A8/A9-induced thromboinflammation in DVT.