| First Author | Amin HZ | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 8065 |
| PubMed ID | 31147569 | Mgi Jnum | J:279900 |
| Mgi Id | MGI:6357549 | Doi | 10.1038/s41598-019-44523-6 |
| Citation | Amin HZ, et al. (2019) CTLA-4 Protects against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice. Sci Rep 9(1):8065 |
| abstractText | 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. |
