ApoB-100-Related Peptide Vaccine Protects Against Angiotensin II-Induced Aortic Aneurysm Formation and Rupture

BACKGROUND T cells and macrophages are implicated in the pathogenesis of aortic aneurysm (AA) and atherosclerosis. We recently demonstrated that a vaccine using an apoB-100-related peptide p210 reduces atherosclerosis with favorable modulation of CD8(+) T cells in apolipoprotein E-deficient (apoE(-/-))mice. OBJECTIVES This study hypothesized that a p210 vaccine could reduce AA formation in the angiotensin II (Ang II)-induced AA model. METHODS Male apoE(-/-) mice were immunized with p210 vaccine and implanted with an Ang II-releasing pump for 4 weeks. Flow cytometry assessed T cell activation and phenotype. Interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) expression were assessed using reverse transcription polymerase chain reaction. We used ex vivo aortic explants to test monocyte adhesion and in vitro cocultures to evaluate CD8(+) T cell function. RESULTS The p210 vaccine activated CD8(+) T cells and reduced AA formation and mortality due to AA rupture, which was attenuated by CD8(+) T cell depletion. Vaccination decreased expression of IL-6 and MCP-1 and reduced macrophage infiltration in the aorta. Cytotoxic T-lymphocyte assay showed that CD8(+) T cells from p210-immunized mice had higher lytic activity against Ang II-stimulated macrophages. The p210 vaccine decreased splenic Th17 cells, and in vitro coculture of CD4(+) and CD8(+) T cells showed that CD8(+) T cells from p210-immunized mice inhibited the polarization of CD4(+) T cells into Th17 cells. IL-17A(-/-) mice infused with a higher dose of Ang II did not develop AA rupture. CONCLUSIONS A p210 vaccine protected against Ang II-induced AA formation and mortality by reducing macrophage infiltration in the aorta and decreasing Th17 cell polarization. Our findings provide a potentially novel immunomodulating approach against AA. (C) 2015 by the American College of Cardiology Foundation.