Endothelial Activation and Repair During Hantavirus Infection: Association with Disease Outcome

Abstract

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.

Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity

“…In adults with sepsis, circulating glycosaminoglycans including HA, was increased in patients with septic shock and was highest in those with a fatal outcome25. Adults with Pumala hantavirus infection had increased syndecan-1 (a marker of endothelial glycocalyx degradation), which was associated with disease severity26. In Vietnamese children with DSS, there was a selective increase in the renal clearance of glycosaminoglycans with increased urinary excretion of HS but not chondroitin-4-sulphate or chondroitin-6-sulphate16.…”

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

“…The mechanisms that are responsible for the more severe and protracted course of DOBV-Sochi infection are not completely understood. Previous studies have demonstrated a role of endothelial activation and repair in the clinical course of PUUV infection [30, 37]. The normalization of clinical parameters has been paralleled to the mobilization of endothelial progenitor cells.…”

Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients

“…[27,32] Neither seems enhanced clearance or pooling of platelets in the enlarged spleen to be involved, as indicated by a previously recorded lack of association of thrombocytopenia and spleen size in PUUV induced HFRS. [33] Endothelial activation markers associate with thrombocytopenia [34] and pathogenic hantaviruses are known to direct the adherence of quiescent platelets through b3-integrin to the surface of infected endothelial cells [35] and specifically to PUUV particles. [36] The adherence of platelets may result in altered platelet activation and decreased circulating platelet count as well as a loss of vascular integrity.…”