The effects of VEGF-A on atherosclerosis, lipoprotein profile, and lipoprotein lipase in hyperlipidaemic mouse models

Abstract

AimsThe 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-/-ApoB100/100 mice.Methods and resultsAfter 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-/-ApoB100/100 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.ConclusionVEGF-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. © 2013 The Author.