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• W2320223412 abstract "Purpose: The role of Vascular Endothelial Growth Factor (VEGF-A) in atherogenesis has remained controversial. The aim of this study was to compare the effects of adenoviral VEGF-A gene transfer on atherosclerosis and lipoproteins in apoE-/-, LDLR-/-,LDLR-/-apoE-/- and LDLR-/-apoB100/100 mice. Methods: After five (lipid metabolism studies) or six (atherosclerosis studies) weeks on Western type diet, systemic adenoviral gene transfers via tail vein was performed with human VEGF-A165 or control vectors. Atherosclerotic lesion area and composition, lipoprotein profiles, plasma lipids and post-heparin plasma lipoprotein lipase (LPL) activity were examined at different time-points. In addition, different tissue samples were collected for mRNA measurements. Results: At day four, VEGF-A induced alterations in lipoprotein profiles compared to LacZ control, and a significant negative correlation was observed between plasma LPL activity and VEGF-A levels. At two weeks, VEGF-A increased total cholesterol levels in LDLR-/-apoB100/100 and LDLR-/- mice. One month after VEGF-A gene transfer, no changes in atherosclerosis were observed in LDLR-/- and LDLR-/-apoB100/100 models, whereas both apoE-/- based models displayed increased en face lesion areas in thoracic and abdominal aortas. VEGF-A also reduced LPL mRNA in heart and White Adipose Tissue (WAT), whereas Angptl4 was increased in WAT, potentially providing further mechanistic explanation for the findings. Conclusions: VEGF-A gene transfer induced pro-atherogenic changes in lipoprotein profiles in all mouse models but increased atherosclerosis only in apoE-/- background. VEGF-A also reduced LPL activity in all studied models, and the effects of VEGF-A on LPL seemed to be mediated through both direct transcriptional regulation and post-translationally by increasing Angptl4. This connection between VEGF-A and LPL is a novel finding and of major importance regarding the clinical use of VEGF-A." @default.
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• W2320223412 date "2013-08-02" @default.
• W2320223412 modified "2023-10-17" @default.
• W2320223412 title "The effects of VEGF-A on atherosclerosis, lipoprotein profile and lipoprotein lipase in hyperlipidemic mouse models" @default.
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• W2320223412 doi "https://doi.org/10.1093/eurheartj/eht308.p2386" @default.
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