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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1095.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Ramona J. Petrovan; Charles D. Kaplan; Ralph A. Reisfeld; Linda K. Curtiss

From the Department of Immunology, The Scripps Research Institute, La Jolla, Calif.

Correspondence to Ramona J. Petrovan, PhD, The Scripps Research Institute, Department of Immunology, IMM-17, 10550 North Torrey Pines Rd, La Jolla, CA 92037. E-mail rjpet{at}scripps.edu

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.

Experimental data indicate that intimal neovascularization plays an important role in development of atherosclerotic lesions. An oral Flk-1-based anti-angiogenic DNA vaccine led to a marked reduction in atherosclerosis in hyperlipidemic LDLr^–/– mice suggesting that genetic immunization may provide an additional treatment choice with long lasting protective effects for this chronic disease.

Key Words: atherosclerosis • vaccination • plaque • endothelium • neovessels

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