title: Elevated vascular endothelial growth factor levels induce hyperpermeability of endothelial cells in hantavirus infection.
abstract: OBJECTIVE
  To investigate the role of vascular endothelial growth factor (VEGF) in haemorrhagic fever with renal syndrome (HFRS).
  
  
  METHODS
  VEGF, soluble VEGF receptor (sVEGFR)-2, angiopoietin (Ang)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels were measured  in serum samples from 68 patients with HFRS. Cultured human umbilical vein endothelial cells (HUEVCs) were infected by Hantaan virus (HTNV) and/or stimulated with recombinant VEGF; dextran permeability of the cells was determined. Claudin-1 and vascular endothelial (VE)-cadherin levels were  determined by real-time reverse transcription-polymerase chain reaction and Western blot analyses.
  
  
  RESULTS
  Serum VEGF, TNF-α and IFN-γ levels were significantly elevated, whereas sVEGFR2 and Ang-1 levels were reduced, during the acute phase of HFRS. In vitro cell  permeability was unaffected by HTNV infection or VEGF stimulation alone, but the combination of HTNV infection and VEGF treatment significantly increased the permeability of endothelial cell monolayers in a time-dependent manner. Claudin-1 and VE-cadherin were downregulated at both the mRNA  and protein level by combined HTNV infection and VEGF stimulation.
  
  
  CONCLUSIONS
  Elevated VEGF induced by HTNV infection may play an important role in the vascular hyperpermeability that is characteristic of HFRS.
authors.affiliation: Centre for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J-P
authors.initials: JP
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: H-T
authors.initials: HT
authors.lastname: Yu
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: P-Z
authors.initials: PZ
authors.lastname: Wang
authors.forename: X-F
authors.initials: XF
authors.lastname: Bai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D018063:Hantaan virus / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000097:blood* / Q000821:virology; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010539:Permeability; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D055815:Young Adult; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D062445:Claudin-1; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; C568108:CLDN1 protein, human; C467484:VEGFA protein, human