Feng Yiting, Zhao Weiqing, Fang Siwen, Zhao Jingwen, Wang Wanshuai, Zhou Shaoyun, Wang Tianyu, Fang Xinke, Chen Xue, Awais Muhammad, Cai Chao, Shen Chuanbin, Liu Ming
Key Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ocean University of China, Chinese Ministry of Education, Qingdao 266000, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266071, China.
Mar Drugs. 2025 Apr 22;23(5):180. doi: 10.3390/md23050180.
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 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.
深静脉血栓形成(DVT)是住院患者中常见的危及生命的并发症。DVT的特征是高凝状态和血栓炎症,其中血小板活化和中性粒细胞胞外陷阱(NET)形成起着关键作用。研究表明,DVT患者中S100A8/A9显著升高,且与血小板活化和NET形成密切相关。岩藻多糖是一种源自墨角藻属藻类的海洋多糖,具有潜在的抗炎和心脏保护作用。我们发现低分子量岩藻多糖(LMF)与S100A8/A9结合,平衡解离常数(KD)为2.368×10 M。LMF在体外抑制S100A8/A9诱导的血小板过度活化和NET形成,并在体内改善DVT,且对止血无明显干扰。我们的结果表明,警报蛋白S100A8/A9是LMF的一个新靶点。LMF在S100A8/A9诱导的DVT血栓炎症中可能具有治疗潜力。