Role of Natural Killer T Cells in Cardiac Remodeling and Failure and the Development of Novel Therapeutic Strategy

Tsutsui Hiroyuki

doi:10.15017/1792721

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. We thus examined whether the activation of iNKT cells might affect the development of LV remodeling and failure. After creation of MI, mice received the injection of either a-galactosylceramide (aGC), the activator of iNKT cells, or phosphate-buffered saline 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI +aGC than MI + PBS. LV cavity dilatation and dysfunction were significantly attenuated inMI +aGC, 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 aGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntiIL-10 receptor antibody abrogated these protective effects of aGC on MI remodeling. The administration of aGC into iNKT cell-deficient Ja18(-/-) mice had no such effects, suggesting that aGC was a specific activator of iNKT cells. iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.

Role of Natural Killer T Cells in Cardiac Remodeling and Failure and the Development of Novel Therapeutic Strategy

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