The Activation of Natural Killer T Cells Ameliorates Post-Infarct Heart Failure in Mice

Abstract

Background: Chronic inflammation has been reported to be involved in the development of cardiac remodeling and failure after myocardial infarction (MI). Natural killer T (NKT) cells have capacity to produce various inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have examined the pathophysiological role of NKT cells in post-MI heart failure. Methods and Results: MI or sham operation was performed in mice. Mice received the intraperitoneal injection of either alpha-galactosylceramide (alpha-GalCer), which specifically activates NKT cells, or vehicle on 1 and 4 days after surgery, and were observed for 28 days. Survival rate was significantly higher in MI+alpha-GalCer than MI. LV cavity dilatation and dysfunction were significantly attenuated in MI+alpha-GalCer, although infarct size was comparable. NKT cell receptor mRNA expression was significantly increased in non-infarcted area of LV from MI compared with sham at only early phase of MI. The injection of alpha-GalCer after MI further enhanced NKT cell receptor expression persistently. In parallel to NKT cell activation, it enhanced LV monocyte chemoattractant protein-1 and tumor necrosis factor-alpha mRNA at 7 days and also interleukin-10 persistently until 28 days. Conclusion: The activation of NKT cell improved survival and ameliorated cardiac remodeling and failure after MI. NKT cell may play a protective role against post-MI heart failure through the enhanced expression of cardioprotective cytokine such as interleukin-10.