title: ApoB-100-related peptide vaccine protects against angiotensin II-induced aortic aneurysm formation and rupture.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Tomoyuki
authors: T
authors: Honjo
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Kuang-Yuh
authors: KY
authors: Chyu
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Paul C
authors: PC
authors: Dimayuga
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Juliana
authors: J
authors: Yano
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Wai Man
authors: WM
authors: Lio
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Portia
authors: P
authors: Trinidad
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Xiaoning
authors: X
authors: Zhao
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Jianchang
authors: J
authors: Zhou
authors: Division of Pediatric Infectious Disease and Immunology, Cedars-Sinai Medical Center, Los Angeles, California.
authors: Shuang
authors: S
authors: Chen
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
authors: Bojan
authors: B
authors: Cercek
authors: Division of Pediatric Infectious Disease and Immunology, Cedars-Sinai Medical Center, Los Angeles, California.
authors: Moshe
authors: M
authors: Arditi
authors: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address: ShahP@cshs.org.
authors: Prediman K
authors: PK
authors: Shah
mesh_terms: D017542:Aneurysm, Ruptured / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D053299:Apolipoprotein B-100 / Q000276:immunology*; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D053299:Apolipoprotein B-100; D014612:Vaccines; D000804:Angiotensin II
keywords: CD8(+) T cells; aortic aneurysm; vaccine