title: The effects of VEGF-A on atherosclerosis, lipoprotein profile, and lipoprotein lipase in hyperlipidaemic mouse models.
abstract: OBJECTIVE
  The role of vascular endothelial growth factor (VEGF-A) in atherogenesis has remained controversial. We addressed this by comparing the effects of adenoviral VEGF-A gene transfer on atherosclerosis and lipoproteins in ApoE(-/-), LDLR(-/-), LDLR(-/-)ApoE(-/-), and LDLR(-/-)ApoB(100/100) mice.
  
  
  RESULTS
  After 4 weeks on western diet, systemic adenoviral gene transfer was performed with hVEGF-A or control vectors. Effects on atherosclerotic lesion area and composition, lipoprotein profiles, and plasma lipoprotein lipase (LPL) activity were examined. On day 4, VEGF-A induced alterations in lipoprotein profiles and a significant negative correlation was observed between plasma LPL activity and VEGF-A levels. One month after gene transfer, no changes in atherosclerosis were observed in LDLR(-/-) and LDLR(-/-)ApoB(100/100) models, whereas both ApoE(-/-) models displayed increased en face lesion areas in thoracic and abdominal aortas. VEGF-A also reduced LPL mRNA in heart and white adipose tissue, whereas Angptl4 was increased, potentially providing further mechanistic explanation for the findings.
  
  
  CONCLUSIONS
  VEGF-A gene transfer induced pro-atherogenic changes in lipoprotein profiles in all models. As a novel finding, VEGF-A also reduced LPL activity, which might underlie the observed changes in lipid profiles. However, VEGF-A was observed to increase atherosclerosis only in the ApoE(-/-) background, clearly indicating some mouse model-specific effects.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Suvi E
authors.initials: SE
authors.lastname: Heinonen
authors.forename: Annukka M
authors.initials: AM
authors.lastname: Kivelä
authors.forename: Jenni
authors.initials: J
authors.lastname: Huusko
authors.forename: Marike H
authors.initials: MH
authors.lastname: Dijkstra
authors.forename: Erika
authors.initials: E
authors.lastname: Gurzeler
authors.forename: Petri I
authors.initials: PI
authors.lastname: Mäkinen
authors.forename: Pia
authors.initials: P
authors.lastname: Leppänen
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Olkkonen
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001055:Apolipoproteins B / Q000172:deficiency / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006949:Hyperlipidemias / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; D042461:Vascular Endothelial Growth Factor A; D008071:Lipoprotein Lipase
keywords: Atherosclerosis; Gene therapy; Genetically altered mice; Lipoprotein lipase; Vascular endothelial growth factor