{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:22:22Z","timestamp":1780615342244,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08046"],"award-info":[{"award-number":["21K08046"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Ministry of Education, Science, and Culture","award":["20117004"],"award-info":[{"award-number":["20117004"]}]},{"name":"The Ministry of Education, Science, and Culture","award":["21390236"],"award-info":[{"award-number":["21390236"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b1-galactosylceramide (\u03b1GC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE\/J\u03b118 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, \u03b1GC 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 \u03b1GC administration significantly increased expressional levels of inflammatory genes such as IFN-\u03b3 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.<\/jats:p>","DOI":"10.3390\/ijms222212451","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T08:53:56Z","timestamp":1637225636000},"page":"12451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Yoshinori","family":"Ohmura","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-6986","authenticated-orcid":false,"given":"Naoki","family":"Ishimori","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimichi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-6648","authenticated-orcid":false,"given":"Takashi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunpei","family":"Horii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Defense Medical College, Namiki 3-2, Tokorozawa 359-0042, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tokuhara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Iwabuchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medicine, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","first-page":"II47","article-title":"Atherosclerotic plaque rupture and thrombosis. 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