Immobility-associated thromboprotection is conserved across mammalian species from bear to human

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.

MeSH terms

  • Animals
  • Blood Platelets* / metabolism
  • Fibrinolytic Agents / therapeutic use
  • HSP47 Heat-Shock Proteins* / metabolism
  • Humans
  • Hypokinesia* / complications
  • Mice
  • Pulmonary Embolism / drug therapy
  • Pulmonary Embolism / ethnology
  • Pulmonary Embolism / metabolism
  • Risk Factors
  • Spinal Cord Injuries* / complications
  • Ursidae* / metabolism
  • Venous Thromboembolism* / etiology
  • Venous Thromboembolism* / metabolism


  • Fibrinolytic Agents
  • HSP47 Heat-Shock Proteins