Abstract 11427: Activation of Invariant Natural Killer T Cells Ameliorates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm Formation in Obese ob/ob Mice

Objective: The infiltration and activation of macrophages and lymphocytes within the vascular wall contribute to the pathogenesis of abdominal aortic aneurysm (AAA). We have demonstrated that invariant natural killer T (iNKT) 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 development of atherosclerosis in obese mice. However, it remains unclear whether iNKT cells are involved also in the development of AAA. Methods and Results: Male obese ob / ob mice were administered angiotensin II (AngII, 1000 ng/kg/min; n=18) or phosphate buffered saline (PBS; n=10) via osmotic minipumps for 4 weeks. AngII-administered mice were further divided into 2 groups; α-galactosylceramide (αGC, 0.1 μg/g body weight intraperitoneal injection; AngII-αGC; n=12), which specifically activates iNKT cells, and PBS (AngII-PBS; n=6). The maximal abdominal aortic diameter was significantly greater in AngII-PBS than in PBS alone (1726±288 vs. 833±69 μm, P P P P P P =NS). Conclusions: AngII induced AAA in obese ob / ob mice in association with activating macrophages as well as T lymphocytes and up-regulating MMP-2 within the vascular tissues, which could be ameliorated by the activation of iNKT cells. Regulation of iNKT cell activation may be a novel therapeutic strategy against AAA.