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Updated: Jul 16, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
DNA vaccination against VEGF receptor 2 reduces atherosclerosis in LDL receptor-deficient mice
Ramona J Petrovan1, Charles D Kaplan, Ralph A Reisfeld
1The Scripps Research Institute, Department of Immunology, IMM-17, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA. rjpet@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.
Insights
An oral DNA vaccine targeting the VEGF receptor 2 (Flk-1) effectively reduced atherosclerosis progression in mice. This approach suppressed neovascularization and demonstrated atheroprotective effects.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Neovascularization in atherosclerosis shares similarities with tumor angiogenesis.
- Antiangiogenic factors targeting tumors may offer therapeutic potential for atherosclerosis.
Purpose of the Study:
- To investigate the efficacy of an oral DNA vaccine against murine VEGF receptor 2 (Flk-1) in preventing or retarding atherosclerosis progression.
- To assess the vaccine's impact on pathological neovascularization in hyperlipidemic LDLr-/- mice.
Main Methods:
- Administration of an oral DNA vaccine targeting Flk-1 in hyperlipidemic LDLr-/- mice.
- Evaluation of T cell activation, neoangiogenesis suppression, and atherosclerosis progression.
- Immunohistochemical analysis of aortic sinus lesions for microvessel density and plaque stability.
Main Results:
- Vaccination induced T cell activation and suppressed neoangiogenesis.
- A significant reduction in atherosclerosis was observed, independent of hypercholesterolemia.
- Decreased lesion area was associated with lower microvessel density but not reduced plaque stability.
Conclusions:
- Targeting activated endothelial cells via a DNA vaccine against Flk-1 offers direct atheroprotective effects.
- This study provides the first evidence for a DNA vaccine's efficacy in treating atherosclerosis by inhibiting neovascularization.