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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Activation of Invariant Natural Killer T Cells by alpha-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese ob/ob Mice
| Title: | Activation of Invariant Natural Killer T Cells by alpha-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese ob/ob Mice |
| Authors: | Saito, Akimichi Browse this author | | Ishimori, Naoki Browse this author →KAKEN DB | | Tokuhara, Satoshi Browse this author | | Homma, Tsuneaki Browse this author | | Nishikawa, Mikito Browse this author | | Iwabuchi, Kazuya Browse this author | | Tsutsui, Hiroyuki Browse this author |
| Keywords: | obesity | | natural killer T cells | | mouse | | macrophages | | inflammation | | angiotensin II | | aortic aneurysm | | alpha-galactosylceramide |
| Issue Date: | 10-May-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in Cardiovascular Medicine |
| Volume: | 8 |
| Start Page: | 659418 |
| Publisher DOI: | 10.3389/fcvm.2021.659418 |
| Abstract: | The 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82141 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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