PMID- 25677313
OWN - NLM
STAT- MEDLINE
DCOM- 20150407
LR  - 20220321
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 65
IP  - 6
DP  - 2015 Feb 17
TI  - ApoB-100-related peptide vaccine protects against angiotensin II-induced aortic 
      aneurysm formation and rupture.
PG  - 546-56
LID - S0735-1097(14)07478-6 [pii]
LID - 10.1016/j.jacc.2014.11.054 [doi]
AB  - 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.
CI  - Copyright (c) 2015 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Honjo, Tomoyuki
AU  - Honjo T
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Chyu, Kuang-Yuh
AU  - Chyu KY
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Dimayuga, Paul C
AU  - Dimayuga PC
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Yano, Juliana
AU  - Yano J
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Lio, Wai Man
AU  - Lio WM
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Trinidad, Portia
AU  - Trinidad P
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Zhao, Xiaoning
AU  - Zhao X
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Zhou, Jianchang
AU  - Zhou J
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Chen, Shuang
AU  - Chen S
AD  - Division of Pediatric Infectious Disease and Immunology, Cedars-Sinai Medical 
      Center, Los Angeles, California.
FAU - Cercek, Bojan
AU  - Cercek B
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California.
FAU - Arditi, Moshe
AU  - Arditi M
AD  - Division of Pediatric Infectious Disease and Immunology, Cedars-Sinai Medical 
      Center, Los Angeles, California.
FAU - Shah, Prediman K
AU  - Shah PK
AD  - Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai 
      Heart Institute, Los Angeles, California. Electronic address: ShahP@cshs.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Apolipoprotein B-100)
RN  - 0 (Vaccines)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
CIN - J Am Coll Cardiol. 2015 Feb 17;65(6):557-9. PMID: 25677314
MH  - Aneurysm, Ruptured/chemically induced/immunology/*prevention & control
MH  - Angiotensin II/toxicity
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/chemically induced/immunology/*prevention & control
MH  - Apolipoprotein B-100/*immunology
MH  - Disease Models, Animal
MH  - Immunity, Cellular
MH  - Macrophages/immunology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - T-Lymphocytes/*immunology
MH  - Vaccines/*therapeutic use
OTO - NOTNLM
OT  - CD8(+) T cells
OT  - aortic aneurysm
OT  - vaccine
EDAT- 2015/02/14 06:00
MHDA- 2015/04/08 06:00
CRDT- 2015/02/14 06:00
PHST- 2014/05/21 00:00 [received]
PHST- 2014/10/22 00:00 [revised]
PHST- 2014/11/11 00:00 [accepted]
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2015/04/08 06:00 [medline]
AID - S0735-1097(14)07478-6 [pii]
AID - 10.1016/j.jacc.2014.11.054 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2015 Feb 17;65(6):546-56. doi: 10.1016/j.jacc.2014.11.054.