Department of Cardiology, University Hospital, LMU Munich, 81377 Munich, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
Science. 2023 Apr 14;380(6641):178-187. doi: 10.1126/science.abo5044. Epub 2023 Apr 13.
Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.
静脉血栓栓塞症（VTE）包括深静脉血栓形成和肺栓塞，是发病率和死亡率的主要原因。短期的与活动受限相关的疾病是 VTE 发展的主要危险因素。矛盾的是，长期处于固定状态的自由冬眠棕熊和瘫痪的脊髓损伤（SCI）患者不会发生 VTE。我们旨在通过跨物种的方法来确定与活动受限相关的 VTE 保护机制。基于质谱的蛋白质组学揭示了冬眠棕熊血小板中的抗血栓形成特征，其中热休克蛋白 47（HSP47）是减少最明显的蛋白质。HSP47 的下调或缺失减弱了免疫细胞的激活和中性粒细胞胞外陷阱的形成，从而为棕熊、SCI 患者和小鼠提供了血栓保护。这种跨物种保守的血小板特征可能会产生抗血栓治疗药物和预后标志物，超越与活动受限相关的 VTE。
