DNA Vaccination Against VEGF Receptor 2 Reduces Atherosclerosis in LDL Receptor–Deficient Mice

Objective— Similarities between neovascular ingrowth in atherosclerotic plaques and angiogenesis in tumors suggest that antiangiogenic factors that target tumor expansion may prove efficacious in the treatment of atherosclerosis. This study examined whether an oral DNA vaccine against the murine VEGF receptor 2 (Flk-1) with demonstrated antitumor effect through inhibition of pathological neovascularization can prevent or retard progression of atherosclerosis in hyperlipidemic low density lipoprotein receptor–deficient (LDLr−/−) mice. Methods and Results— Vaccination against Flk-1 resulted in T cell activation, suppression of neoangiogenesis, and a marked reduction in atherosclerosis which was independent of hypercholesterolemia in both male and female mice. Immunohistochemical characterization of aortic sinus lesions showed that the decreased lesion area was not associated with reduced plaque stability and had a lower density of microvessels. Conclusions— These findings demonstrate for the first time that a DNA vaccine targeting activated endothelial cells in atherosclerotic lesions provides direct atheroprotective effects.