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Heparanase expression and activity are increased in platelets during clinical sepsis
Alicia S Eustes1,2,3, Robert A Campbell1, Elizabeth A Middleton1
1Department of Internal Medicine and Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA.
Heparanase (HPSE) levels and activity increase in human platelets during sepsis. Elevated active HPSE in platelets is linked to increased mortality in septic patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Heparanase (HPSE) degrades heparan sulfate, a key component of the endothelial glycocalyx.
- HPSE contributes to endothelial barrier dysfunction and mortality during sepsis.
- Platelets are a significant source of HPSE in the body.
Purpose of the Study:
- To investigate if HPSE expression and activity increase in human platelets during clinical sepsis.
- To examine the association between platelet HPSE levels and clinical outcomes in septic patients.
Main Methods:
- HPSE expression and activity were measured in platelets from septic patients and healthy donors.
- Techniques included transcriptomic, proteomic, and functional enzymatic assays.
- Septic patients were monitored for mortality, with prospective data collection.
Main Results:
- HPSE mRNA expression and protein synthesis were significantly upregulated in platelets during sepsis.
- Both pro- and active forms of HPSE increased, but only active HPSE correlated with mortality.
- HPSE enzymatic activity was also elevated in platelets from septic patients.
Conclusions:
- HPSE translation and enzymatic activity increase in human platelets during sepsis.
- Elevated active HPSE in platelets is associated with sepsis-related mortality.
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