Vaccination Against VEGFR2 Attenuates Initiation and Progression of Atherosclerosis
| Autor: | Paul H.A. Quax, Gijs H.M. van Puijvelde, Paula de Vos, Johan Kuiper, Erik A.L. Biessen, Theo J.C. Van Berkel, Niels Peterse, Arnaud D. Hauer, Vincent van Weel, Ralph A. Reisfeld, Eva J.A. van Wanrooij, Andreas G. Niethammer |
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| Rok vydání: | 2007 |
| Předmět: |
Cellular immunity
Angiogenesis Hypercholesterolemia Administration Oral CD8-Positive T-Lymphocytes DNA vaccination Mice Ischemia Vaccines DNA Animals Medicine Cytotoxic T cell Immunity Cellular Neovascularization Pathologic Histocytochemistry business.industry Vascular disease Endothelial Cells Immunotherapy Active Kinase insert domain receptor respiratory system Atherosclerosis medicine.disease Vascular Endothelial Growth Factor Receptor-2 Coculture Techniques Hindlimb Vaccination Immunology cardiovascular system Female Cardiology and Cardiovascular Medicine business CD8 |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 27:2050-2057 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | 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. Methods and 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. |
| Databáze: | OpenAIRE |
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