Abstract 14337: The Disruption of Natural Killer T Cell Receptor Exacerbates Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice
Background Natural killer T (NKT) cells play an important role in tissue inflammation in various diseases due to their capacity to produce inflammatory cytokines and orchestrate tissue inflammation. We previously demonstrated that the activation of NKT cells by α-galactosylceramide attenuated the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI), which was mediated by the enhanced expression of interleukin-10 (IL-10) in the heart. We thus hypothesized that the disruption of NKT cell receptor could further exacerbate this deleterious process.
Methods MI was created in NKT cell receptor knockout (KO) and wild-type (WT) mice by ligating the left coronary artery, and sham operation was also performed. Four groups of mice, WT+sham (n=10), KO+sham (n=10), WT+MI (n=25), and KO+MI (n=35), were observed for 28 days. Echocardiography, hemodynamic measurements, and histological analysis were performed. RT-PCR was performed to quantify mRNA expression in LV tissues from non-infarcted area.
Results Heart rate and blood pressure were comparable among groups. LV end-diastolic dimension was greater (5.4±0.04 vs 5.7±0.1 mm, p<0.05), and LV fractional shortening was smaller (16.5±0.4 vs 13.6±0.3 %, p<0.05) in KO+MI than WT+MI, with no significant changes in infarct size (55.7±2% vs 57.7±0.4%, P=NS). LV end-diastolic pressure and lung weight/body weight were higher in KO+MI than in WT+MI. Such changes were not observed in sham groups. Myocyte hypertrophy, interstitial fibrosis, and apoptosis were present in WT+MI and further exacerbated in KO+MI. Tumor necrosis factor-α (TNF-α) mRNA expression was significantly decreased, and interestingly IL-10 mRNA expression was completely abolished in KO+MI compared to WT+MI (relative value of WT+sham: TNF-α 0.3±0.1 vs 0.8±0.2, P<0.05 and IL-10 0.0±0.0 vs 0.9±0.2, P<0.05). Monocyte chemoattractant protein-1 and F4/80 mRNA expression between WT+MI and KO+MI did not differ.
Conclusions The disruption of NKT cell receptor exacerbated LV remodeling and failure after MI through the diminished expression of cardioprotective cytokine, IL-10. NKT cell may play a cardioprotective role against the development and progression of post-MI heart failure.
- © 2011 by American Heart Association, Inc.