2024-03-28T12:52:58Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/821412022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121Activation of Invariant Natural Killer T Cells by alpha-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese ob/ob MiceSaito, Akimichi1000070399848Ishimori, NaokiTokuhara, SatoshiHomma, TsuneakiNishikawa, MikitoIwabuchi, KazuyaTsutsui, Hiroyukimetadata only accessobesitynatural killer T cellsmousemacrophagesinflammationangiotensin IIaortic aneurysmalpha-galactosylceramide490The infiltration and activation of macrophages as well as lymphocytes within the aorta contribute to the pathogenesis of abdominal aortic aneurysm (AAA). Invariant natural killer T (iNKT) cells are unique subset of T lymphocytes and have a crucial role in atherogenesis. However, it remains unclear whether iNKT cells also impact on the development of AAA. Ob/ob mice were administered angiotensin II (AngII, 1,000 ng/kg/min) or phosphate-buffered saline (PBS) by osmotic minipumps for 4 weeks and further divided into 2 groups; alpha-galactosylceramide (alpha GC; PBS-alpha GC; n = 5 and AngII-alpha GC; n = 12), which specifically activates iNKT cells, and PBS (PBS-PBS; n = 10, and AngII-PBS; n = 6). Maximal abdominal aortic diameter was comparable between PBS-PBS and PBS-alpha GC, and was significantly greater in AngII-PBS than in PBS-PBS. This increase was significantly attenuated in AngII-alpha GC without affecting blood pressure. alpha GC significantly enhanced iNKT cell infiltration compared to PBS-PBS. The ratio of F4/80-positive macrophages or CD3-positive T lymphocytes area to the lesion area was significantly higher in AngII-PBS than in PBS-PBS, and was significantly decreased in AngII-alpha GC. Gene expression of M2-macrophage specific markers, arginase-1 and resistin-like molecule alpha, was significantly greater in aortic tissues from AngII-alpha GC compared to AngII-PBS 1 week after AngII administration, and this increase was diminished at 4 weeks. Activation of iNKT cells by alpha GC can attenuate AngII-mediated AAA in ob/ob mice via inducing anti-inflammatory M2 polarized state. Activation of iNKT cells by the bioactive lipid alpha GC may be a novel therapeutic target against the development of AAA.Frontiers Media2021-05-10engjournal articleNAhttp://hdl.handle.net/2115/82141https://doi.org/10.3389/fcvm.2021.6594182297-055XFrontiers in Cardiovascular Medicine8659418