CTLA-4 Protects against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice Article Swipe
Hilman Zulkifli Amin
,
Naoto Sasaki
,
Tomoya Yamashita
,
Taiji Mizoguchi
,
Tomohiro Hayashi
,
Takuo Emoto
,
Takuya Matsumoto
,
Naofumi Yoshida
,
Tokiko Tabata
,
Sayo Horibe
,
Shoji Kawauchi
,
Yoshiyuki Rikitake
,
Ken‐ichi Hirata
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-019-44523-6
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-019-44523-6
Vascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown. We determined the effects of CTLA-4 overexpression on experimental AAA. We continuously infused CTLA-4 transgenic (CTLA-4-Tg)/apolipoprotein E–deficient ( Apoe −/− ) mice or control Apoe −/− mice fed a high-cholesterol diet with angiotensin II by implanting osmotic mini-pumps and evaluated the development of AAA. Ninety percent of angiotensin II-infused mice developed AAA, with 50% mortality because of aneurysm rupture. Overexpression of CTLA-4 significantly reduced the incidence (66%), mortality (26%), and diameter of AAA. These protective effects were associated with a decreased number of effector CD4 + T cells and the downregulated expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, on CD11c + dendritic cells in lymphoid tissues. CTLA-4-Tg/ Apoe −/− mice had reduced accumulation of macrophages and CD4 + T cells, leading to attenuated aortic inflammation, preserved vessel integrity, and decreased susceptibility to AAA and aortic rupture. Our findings suggest T-cell coinhibitory molecule CTLA-4 as a novel therapeutic target for AAA.
Related Topics
Concepts
CD80
Angiotensin II
Cytotoxic T cell
CD86
T cell
CTLA-4
Immune system
Inflammation
Immunology
Medicine
CD11c
Chemistry
Biology
Internal medicine
CD40
Receptor
Biochemistry
Phenotype
Gene
In vitro
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-019-44523-6
- https://www.nature.com/articles/s41598-019-44523-6.pdf
- OA Status
- gold
- Cited By
- 29
- References
- 27
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2947023146
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2947023146Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-019-44523-6Digital Object Identifier
- Title
-
CTLA-4 Protects against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in MiceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-05-30Full publication date if available
- Authors
-
Hilman Zulkifli Amin, Naoto Sasaki, Tomoya Yamashita, Taiji Mizoguchi, Tomohiro Hayashi, Takuo Emoto, Takuya Matsumoto, Naofumi Yoshida, Tokiko Tabata, Sayo Horibe, Shoji Kawauchi, Yoshiyuki Rikitake, Ken‐ichi HirataList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-019-44523-6Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-019-44523-6.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-019-44523-6.pdfDirect OA link when available
- Concepts
-
CD80, Angiotensin II, Cytotoxic T cell, CD86, T cell, CTLA-4, Immune system, Inflammation, Immunology, Medicine, CD11c, Chemistry, Biology, Internal medicine, CD40, Receptor, Biochemistry, Phenotype, Gene, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
29Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 6, 2023: 3, 2022: 6, 2021: 5Per-year citation counts (last 5 years)
- References (count)
-
27Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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