Vaccination against VEGFR2 attenuates initiation and progression of atherosclerosis.
OBJECTIVE
Vascular endothelial growth factor receptor 2 (VEGFR2)-overexpressing cells may form an interesting target for the treatment of atherosclerosis because of their involvement in processes that contribute to this disease, such as angiogenesis.


RESULTS
We vaccinated mice against VEGFR2 by an orally administered DNA vaccine, comprising a plasmid, encoding murine VEGFR2, carried by live attenuated Salmonella typhimurium. This vaccine induces cellular immunity against cells that overexpress VEGFR2. Vaccination of hypercholesterolemic mice against VEGFR2 resulted in a marked induction of CD8+ cytotoxic T cells specific for VEGFR2 and led to an inhibition of angiogenesis in a hindlimb ischemia model. Interestingly, VEGFR2 vaccination attenuated the progression of preexisting advanced atherosclerotic lesions in the brachiocephalic artery of apoE-/- mice. Furthermore, VEGFR2 vaccination strongly reduced the initiation of collar-induced atherosclerosis in the carotid arteries of LDLr-/- mice. In addition, denudation of the carotid artery, as a model for postinterventional lesion formation, resulted in delayed endothelial replacement and significantly increased neointima formation on VEGFR2 vaccination.


CONCLUSIONS
These data indicate the prominent role of VEGFR2+ cells in cardiovascular diseases and show that induction of cellular immunity against atherosclerosis-associated cells by means of DNA vaccination may contribute to the development of novel therapies against atherosclerosis.
Hauer
Arnaud D
AD
Division of Biopharmaceutics, Leiden University, The Netherlands. A.Hauer@LACDR.leidenuniv.nl
van Puijvelde
Gijs H M
GH
Peterse
Niels
N
de Vos
Paula
P
van Weel
Vincent
V
van Wanrooij
Eva J A
EJ
Biessen
Erik A L
EA
Quax
Paul H A
PH
Niethammer
Andreas G
AG
Reisfeld
Ralph A
RA
van Berkel
Theo J C
TJ
Kuiper
Johan
J
D000284:Administration, Oral; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006614:Hindlimb; D006651:Histocytochemistry; D006937:Hypercholesterolemia / Q000628:therapy*; D007111:Immunity, Cellular / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D007511:Ischemia / Q000628:therapy; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2