title: Gene transfers of vascular endothelial growth factor-A, vascular endothelial growth factor-B, vascular endothelial growth factor-C, and vascular endothelial growth factor-D have no effects on atherosclerosis in hypercholesterolemic low-density lipoprotein-receptor/apolipoprotein B48-deficient mice.
abstract: BACKGROUND
  The role of vascular endothelial growth factors (VEGFs) in large arteries has been proposed to be either vasculoprotective or proatherogenic. Because VEGF family members are used for human therapy, it is important to know whether they could enhance atherogenesis. We tested the effects of the members of the VEGF gene family on atherogenesis in LDL-receptor/apolipoprotein (apo) B48 double-knockout (LDLR/apoB48) mice using systemic adenoviral gene transfer.
  
  
  RESULTS
  Six groups of LDLR/apoB48-deficient mice (n=110) were kept 3 months on a Western-type diet. After 6 weeks of diet, mice were injected via tail vein with recombinant adenoviruses expressing VEGF-A, -B, -C, or -D or LacZ (1 x 10(9) PFU) or rhVEGF-A protein (2 microg/kg) and euthanized 6 weeks later. Also, older mice (n=36) were injected after 4 months on the diet and euthanized 6 weeks later (total time on the diet, 22 weeks) to evaluate the effects of gene transfers on the development of more mature lesions. Aortas were analyzed for the presence of macroscopic lesions, cross-sectional lesion areas, neovascularization, and cellular composition of the lesions. All groups had equivalent plasma cholesterol and triglyceride levels. Gene transfers with recombinant adenoviruses or administration of rhVEGF-A protein had no statistically significant effects on en face atherosclerotic lesions in the aorta, cross-sectional lesion area, neovascularization, or cellular composition of the lesions.
  
  
  CONCLUSIONS
  This study shows no proatherogenic effects of adenovirus-mediated gene transfers of VEGF-A, -B, -C, or -D in the LDLR/apoB48-deficient hypercholesterolemic mice, in which lipoprotein profile and atherosclerosis closely resemble those in human disease.
authors.affiliation: Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Leppänen
authors.forename: Suvi
authors.initials: S
authors.lastname: Koota
authors.forename: Ivana
authors.initials: I
authors.lastname: Kholová
authors.forename: Jonna
authors.initials: J
authors.lastname: Koponen
authors.forename: Christina
authors.initials: C
authors.lastname: Fieber
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology*; D022761:Gene Transfer, Horizontal; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D008055:Lipids / Q000097:blood; D051379:Mice; D018919:Neovascularization, Physiologic; D011973:Receptors, LDL / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics
chemical_list: D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008055:Lipids; D011973:Receptors, LDL; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D