Abstract 11636: Natural Killer T Cells are Involved in the Development of Experimental Aortic Aneurysm and Dissection in Apolipoprotein-E Deficient Mice
Objective: The infiltration and activation of macrophages as well as lymphocytes within the vascular wall may contribute to the pathogenesis of aortic aneurysm and dissection. Natural killer T (NKT) cells, a unique subset of T lymphocytes which recognize glycolipid antigens and secrete a large amount of TH1/TH2 cytokines on activation, have a crucial role in the atherogenesis. However, it remains undetermined whether NKT cells are also involved in the development of aortic aneurysm.
Methods and Results: Male apolipoprotein-E deficient mice were infused with angiotensin II (1000 ng/kg/min) via osmotic minipumps and divided into 2 groups according to the co-administration of OCH (0.1 μ g/g body weight, twice a week; n=10), a specific activator of NKT cells, or phosphate-buffered saline (PBS; n=15) for 4 weeks. The structural changes of the suprarenal abdominal aorta were assessed by the histological analysis. Activation of NKT cells by OCH significantly increased the maximal aortic diameter (2042±327 vs. 1337±75 μ m, p<0.01) and the incidence of dissection (57 vs. 8%, p<0.05) compared to PBS-treated mice without affecting the systolic arterial blood pressure (140±5 vs. 138±5 mmHg, p=NS). Immunohistochemical staining revealed that OCH markedly enhanced the infiltration of Mac-2+ macrophages and CD3+ T lymphocytes by 8.2-folds and 5.4-folds (p<0.05 each), respectively within the media and adventitia of the aortic wall. Real-time PCR showed that OCH significantly increased the mRNA expression of interferon (IFN)-γ by 2.6-folds (p<0.05) and also enhanced the expression of metalloproteinase-9 (MMP-9) by 1.5-folds in the aorta compared to PBS-treated mice.
Conclusions: NKT cells are involved in the development of aortic aneurysm and dissection via activating macrophage and T lymphocyte infiltration and up-regulation of IFN-γ and MMP-9 within the vascular tissues. Regulation of NKT cell activation may be a novel therapeutic strategy against aortic aneurysm and dissection.
- © 2011 by American Heart Association, Inc.