title: Systemic production of vascular endothelial growth factor and fms-like tyrosine kinase-1 receptor in acute Kawasaki disease.
abstract: BACKGROUND
  Increased vascular permeability is an important event during the initial process of Kawasaki disease (KD). One potential responsible candidate for the induction of vascular hyperpermeability is vascular endothelial growth factor (VEGF).
  
  
  RESULTS
  We investigated the expression of VEGF and its receptors (flt-1, KDR) in acute KD tissues at 7 days to 5 weeks of illness. Neuropilin-1, which enhances the binding of VEGF(165) to KDR, was also studied. Abundant expression of VEGF and flt-1 was documented immunohistochemically in many organs from acute KD, including heart and lung. VEGF and flt-1 were colocalized in all vessels that showed edema. These molecules resided in endothelium and vascular media and also in migrating smooth muscle cells in neointima and infiltrating macrophages. Compared with controls, coronary vessels of acute KD had upregulation of VEGF and flt-1 but not KDR or neuropilin-1. KDR was expressed by vessels at 7 days of illness but not later in the illness. Plasma proteins were more extensively bound to the extracellular matrix in coronary vessels in acute KD than controls. Furthermore, elevation of serum VEGF levels was correlated with low serum albumin in acute KD (n=220, r=-0.53, P<0.001).
  
  
  CONCLUSIONS
  These findings suggest that VEGF and flt-1 are upregulated in blood vessels in many organs of acute KD. Expression of KDR was limited to the early stage of acute KD. The roles of VEGF in acute KD may involve promotion of vascular permeability and macrophage activation. Low serum albumin may indicate overproduction of VEGF in acute KD.
authors.affiliation: Department of Pediatrics, Kawasaki Seitetsu Hospital, Chiba, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Yasukawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Terai
authors.forename: Stanford T
authors.initials: ST
authors.lastname: Shulman
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toyozaki
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Yajima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kohno
authors.forename: Anne H
authors.initials: AH
authors.lastname: Rowley
mesh_terms: D000208:Acute Disease; D000783:Aneurysm / Q000378:metabolism / Q000473:pathology; D044466:Asian People; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004487:Edema / Q000209:etiology / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000097:blood; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007564:Japan; D008222:Lymphokines / Q000096:biosynthesis* / Q000097:blood; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D039942:Neuropilin-1; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D012016:Reference Values; D012709:Serum Albumin / Q000172:deficiency / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D044465:White People
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D005337:Fibrin; D005340:Fibrinogen; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1