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Hokkaido University Collection of Scholarly and Academic Papers >
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Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
| Title: | Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice |
| Authors: | Ohmura, Yoshinori Browse this author | | Ishimori, Naoki Browse this author →KAKEN DB | | Saito, Akimichi Browse this author | | Yokota, Takashi Browse this author →KAKEN DB | | Horii, Shunpei Browse this author | | Tokuhara, Satoshi Browse this author | | Iwabuchi, Kazuya Browse this author | | Tsutsui, Hiroyuki Browse this author |
| Keywords: | alpha-galactosylceramide | | apolipoprotein E knockout mice | | atherosclerosis | | brachiocephalic artery | | macrophages | | matrix metalloproteinase | | natural killer T cells | | plaque instability |
| Issue Date: | Nov-2021 |
| Publisher: | MDPI |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 22 |
| Issue: | 22 |
| Start Page: | 12451 |
| Publisher DOI: | 10.3390/ijms222212451 |
| Abstract: | The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of alpha-galactosylceramide (alpha GC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/J alpha 18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, alpha GC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that alpha GC administration significantly increased expressional levels of inflammatory genes such as IFN-gamma and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/85254 |
| 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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