Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice

Mochamad Ali Sobirin, Shintaro Kinugawa, Masashige Takahashi, Arata Fukushima, Tsuneaki Homma, Taisuke Ono, Kagami Hirabayashi, Tadashi Suga, Putri Azalia, Shingo Takada, Masaru Taniguchi, Toshinori Nakayama, Naoki Ishimori, Kazuya Iwabuchi, Hiroyuki Tsutsui

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Abstract

Rationale: 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 (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% versus 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 noninfarcted 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. AntienIL-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.

Original languageEnglish
Pages (from-to)1037-1047
Number of pages11
JournalCirculation research
Volume111
Issue number8
DOIs
Publication statusPublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Sobirin, M. A., Kinugawa, S., Takahashi, M., Fukushima, A., Homma, T., Ono, T., Hirabayashi, K., Suga, T., Azalia, P., Takada, S., Taniguchi, M., Nakayama, T., Ishimori, N., Iwabuchi, K., & Tsutsui, H. (2012). Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice. Circulation research, 111(8), 1037-1047. https://doi.org/10.1161/CIRCRESAHA.112.270132