Deregulation of levels of angiopoietin-1 and angiopoietin-2 is associated with severe courses of hantavirus infection

Abstract

BackgroundHantavirus disease is characterized by endothelial dysfunction. Angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) play a key role in the control of capillary permeability. Ang-1 is responsible for maintenance of cell-to-cell contacts whereas Ang-2 destabilizes monolayers. An imbalance of Ang-1 and Ang-2 levels results in enhanced permeability and capillary leakage. ObjectivesTo analyze the involvement of angiopoietins in hantavirus-induced disruption of endothelia, we measured the levels of Ang-1 and Ang-2 in hantavirus infection. Study designLevels of angiopoietins of 31 patients with acute Puumala virus (PUUV) infection and a patient infected with Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi) were analyzed. An age-matched group of 16 healthy volunteers served as control. The ratios of Ang-2 to Ang-1 levels were calculated and correlated with laboratory parameters. ResultsPatients with PUUV and DOBV-Sochi infection exhibited elevated ratios of Ang-2/Ang-1 compared to the control group. The imbalance of Ang-2 to Ang-1 levels was observed early after onset of symptoms and lasted for the acute phase of infection. The deregulation in DOBV-Sochi infection was more prominent than in PUUV infection. Analysis of Ang-2/Ang-1 ratio and laboratory parameters in the PUUV cohort revealed a positive correlation with serum creatinine and a negative correlation with serum albumin and thrombocyte levels. ConclusionsWe observed an imbalance between levels of Ang-1 and Ang-2 in patients infected with PUUV and DOBV-Sochi. Elevated Ang-2/Ang-1 ratios correlate with disease severity. The virus-induced deregulation of angiopoietin levels may enhance capillary permeability and contribute to the pathogenesis of hantavirus disease.