2024-03-29T05:51:49Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/522732022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121Activation of Natural Killer T Cells Ameliorates Postinfarct Cardiac Remodeling and Failure in MiceSobirin, Mochamad AliKinugawa, ShintaroTakahashi, MasashigeFukushima, ArataHomma, TsuneakiOno, TaisukeHirabayashi, KagamiSuga, TadashiAzalia, PutriTakada, ShingoTaniguchi, MasaruNakayama, ToshinoriIshimori, NaokiIwabuchi, KazuyaTsutsui, Hiroyukinatural killer T cellsmyocardial infarctioninflammationheart failurecytokines493Rationale: Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling. Objective: The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure. Methods and Results: After creation of MI, mice received the injection of either α-galactosylceramide (αGC; n=27), the activator of iNKT cells, or phosphate-buffered saline (PBS; n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+αGC than MI+PBS (59% vs 32%, P<0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+αGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in non-infarcted LV from MI and αGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. Anti IL-10 receptor antibody abrogated these protective effects of αGC on MI remodeling. The administration of αGC into iNKT cell-deficient Jα18^[-/-] mice had no such effects, suggesting that αGC was a specific activator of iNKT cells. Conclusions: iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.American Heart AssociationJournal Articleapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/52273https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/52273/2/CR111-8_1037-1047.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/52273/1/Data_Supplement.pdf0009-7330Circulation Research1118103710472012-09-28enginfo:pmid/22887770info:doi/10.1161/CIRCRESAHA.112.270132author