Document Detail


The Activation of Natural Killer T Cells Ameliorates Post-Infarct Cardiac Remodeling and Failure in Mice.
MedLine Citation:
PMID:  22887770     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (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.
Authors:
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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-10
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Hokkaido University, and Diponegoro University;
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