Endothelial activation and repair during hantavirus infection: association with disease outcome.
BACKGROUND
Endothelial activation and dysfunction play a central role in the pathogenesis of sepsis and viral hemorrhagic fevers. Hantaviral disease is a viral hemorrhagic fever and is characterized by capillary dysfunction, although the underlying mechanisms for hantaviral disease are not fully elucidated.


METHODS
The temporal course of endothelial activation and repair were analyzed during Puumala hantavirus infection and associated with disease outcome and a marker for hypoxia, insulin-like growth factor binding protein 1 (IGFBP-1). The following endothelial activation markers were studied: endothelial glycocalyx degradation (syndecan-1) and leukocyte adhesion molecules (soluble vascular cellular adhesion molecule 1, intercellular adhesion molecule 1, and endothelial selectin). Cytokines associated with vascular repair were also analyzed (vascular endothelial growth factor, erythropoietin, angiopoietin, and stromal cell-derived factor 1).


RESULTS
Most of the markers we studied were highest during the earliest phase of hantaviral disease and associated with clinical and laboratory surrogate markers for disease outcome. In particular, the marker for glycocalyx degradation, syndecan-1, was significantly associated with levels of thrombocytes, albumin, IGFBP-1, decreased blood pressure, and disease severity.


CONCLUSIONS
Hantaviral disease outcome was associated with endothelial dysfunction. Consequently, the endothelium warrants further investigation when designing future medical interventions.
Division of Infectious Diseases, Department of Clinical Microbiology , Umeå University , Umeå , Sweden.
Anne-Marie
AM
Connolly-Andersen
Division of Infectious Diseases, Department of Clinical Microbiology , Umeå University , Umeå , Sweden.
Therese
T
Thunberg
Division of Infectious Diseases, Department of Clinical Microbiology , Umeå University , Umeå , Sweden.
Clas
C
Ahlm
Puumala virus; endothelial activation; endothelial surface layer; endothelium; glycocalyx; hantavirus; hemorrhagic fever with renal syndrome; vasculogenesis/angiogenesis