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. METHODS AND 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.
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. METHODS AND 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 hypercholesterolemicmice, in which lipoprotein profile and atherosclerosis closely resemble those in human disease.
Authors: Andrea Caporali; Magnus Bäck; Mat J Daemen; Imo E Hoefer; Elizabeth A Jones; Esther Lutgens; Christian M Matter; Marie-Luce Bochaton-Piallat; Arndt F Siekmann; Judith C Sluimer; Sabine Steffens; José Tuñón; Cecile Vindis; Jolanda J Wentzel; Seppo Ylä-Herttuala; Paul C Evans Journal: Cardiovasc Res Date: 2018-09-01 Impact factor: 10.787
Authors: Carolina E Hagberg; Annelie Falkevall; Xun Wang; Erik Larsson; Jenni Huusko; Ingrid Nilsson; Laurens A van Meeteren; Erik Samen; Li Lu; Maarten Vanwildemeersch; Joakim Klar; Guillem Genove; Kristian Pietras; Sharon Stone-Elander; Lena Claesson-Welsh; Seppo Ylä-Herttuala; Per Lindahl; Ulf Eriksson Journal: Nature Date: 2010-03-14 Impact factor: 49.962
Authors: Antti Saraste; Iina Laitinen; Eliane Weidl; Moritz Wildgruber; Axel W Weber; Stephan G Nekolla; Gabriele Hölzlwimmer; Irene Esposito; Axel Walch; Pia Leppänen; Irina Lisinen; Peter B Luppa; Seppo Ylä-Herttuala; Hans-Jürgen Wester; Juhani Knuuti; Markus Schwaiger Journal: J Nucl Cardiol Date: 2012-04-20 Impact factor: 5.952
Authors: Maria G Stathopoulou; Amélie Bonnefond; Ndeye Coumba Ndiaye; Mohsen Azimi-Nezhad; Said El Shamieh; Abdelsalam Saleh; Marc Rancier; Gerard Siest; John Lamont; Peter Fitzgerald; Sophie Visvikis-Siest Journal: J Lipid Res Date: 2012-12-02 Impact factor: 5.922
Authors: Iina Laitinen; Päivi Marjamäki; Kjell Någren; V Jukka O Laine; Ian Wilson; Pia Leppänen; Seppo Ylä-Herttuala; Anne Roivainen; Juhani Knuuti Journal: Eur J Nucl Med Mol Imaging Date: 2008-08-19 Impact factor: 9.236