CD8 + T-cell deficiency protects mice from abdominal aortic aneurysm formation in response to calcium chloride 2

• Published in: Journal of hypertension Vol. 42; no. 11; p. 1966
• Main Authors: Lin, Zhuo, Zhao, Mantong, Zhang, Xian, Piao, Jinshun, Zheng, Xintong, Shu, Shangzhi, Zhao, Longguo, Zhang, Meiping, Shi, Guo-Ping, Lei, Yanna, Cui, Rihua, Yue, Xueling, Cheng, Xian Wu
• Format: Journal Article
• Language: English
• Published: Netherlands 01.11.2024
• Subjects: Animals; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - prevention & control; Calcium Chloride; CD8-Positive T-Lymphocytes; Disease Models, Animal; Interferon-gamma - metabolism; Male; Matrix Metalloproteinase 2 - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress
• DOI: 10.1097/HJH.0000000000003823

Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8 + T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive. Eight-week-old male wildtype (CD8 +/+ ) and Cd8a knockout (CD8 -/- ) mice were used in a calcium chloride 2 (CaCl 2 )-induced experimental AAA model. At 6 weeks after surgery, CD8 + T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1β, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91 phox ], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8 + T cells of IFN-γ +/+ mice diminished CD8 -/- -mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells. The vasculoprotective effects of CD8 + T-cell deletion in a mouse CaCl 2 -induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8 + T-cell-derived IFN-γ secretion.