title: Vascular endothelial growth factor-D expression in human atherosclerotic lesions.
abstract: OBJECTIVE
  Vascular endothelial growth factor-D (VEGF-D) is a recently characterized member of the VEGF family, but its expression in atherosclerotic lesions remains unknown. We studied the expression of VEGF-D and its receptors (VEGFR-2 and VEGFR-3) in normal and atherosclerotic human arteries, and compared that to the expression pattern of VEGF-A.
  
  
  METHODS
  Human arterial samples (n=39) obtained from amputation operations and fast autopsies were classified according to the stage of atherosclerosis and studied by immunohistochemistry. The results were confirmed by in situ hybridization and RT-PCR.
  
  
  RESULTS
  We found that while VEGF-A expression increased during atherogenesis, VEGF-D expression remained relatively stable only decreasing in complicated lesions. In normal arteries and in early lesions VEGF-D was mainly expressed in smooth muscle cells, whereas in complicated atherosclerotic lesions the expression was most prominent in macrophages and also colocalized with plaque neovascularization. By comparing the staining profiles of different antibodies, we found that proteolytic processing of VEGF-D was efficient in the vessel wall. VEGFR-2, but not VEGFR-3, was expressed in the vessel wall at every stage of atherosclerosis.
  
  
  CONCLUSIONS
  Our results suggest that in large arteries VEGF-D is mainly expressed in smooth muscle cells and that it may have a role in the maintenance of vascular homeostasis. However, in complicated lesions it was also expressed in macrophages and may contribute to plaque neovascularization. The constitutive expression of VEGFR-2 in arteries suggests that it may be one of the principal mediators of the VEGF-D effects in large arteries.
authors.affiliation: Department of Molecular Medicine, AI Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Rutanen
authors.forename: Pia
authors.initials: P
authors.lastname: Leppänen
authors.forename: Tiina T
authors.initials: TT
authors.lastname: Tuomisto
authors.forename: Tuomas T
authors.initials: TT
authors.lastname: Rissanen
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Hiltunen
authors.forename: Ismo
authors.initials: I
authors.lastname: Vajanto
authors.forename: Mari
authors.initials: M
authors.lastname: Niemi
authors.forename: Tomi
authors.initials: T
authors.lastname: Häkkinen
authors.forename: Kari
authors.initials: K
authors.lastname: Karkola
authors.forename: Steven A
authors.initials: SA
authors.lastname: Stacker
authors.forename: Marc G
authors.initials: MG
authors.lastname: Achen
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis* / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3