Abstract 8829: The Disruption of Natural Killer T Cell Exacerbates Cardiac Hypertrophy and Heart Failure Due to Pressure Overload in Mice
Background Chronic inflammation has been reported to be involved in the development of cardiac remodeling and failure. Natural killer T (NKT) cells, a subset of T lymphocytes, have capacity to produce various inflammatory cytokines and orchestrate tissue inflammation. Our previous study demonstrated that the pharmacological activation of NKT cells attenuated the development of heart failure (HF), which was mediated by the enhanced expression of interleukin-10. However, no previous studies have examined the pathophysiological role of NKT cells in pressure overload-induced HF. We thus hypothesized that the disruption of NKT cell could exacerbate cardiac hypertrophy and HF after pressure overload in mice.
Methods Transverse aortic constriction (TAC) operation was performed in male C57BL/6J wild-type(WT) and NKT cell knockout (KO) mice, and sham operation was also performed; WT+Sham (n=5), KO+sham (n=5), WT+TAC (n=29), and KO+TAC (n=34). After 14 days, echocardiography was performed, and gene expressions in left ventricle (LV) tissues were quantified by RT-PCR.
Results Survival rate during 28 days was significantly lower in KO+TAC than WT+TAC (16% vs. 61%, P<0.05), and no mice died in sham groups. NKT cell receptor was increased by 60% in LV from TAC compared to Sham at 14days. LV end-diastolic dimension (4.60±0.14vs3.57±0.08 mm, p<0.05) were greater, and LV fractional shortening (17.1±0.8 vs 30.4±4.3 %, p<0.05) was lower in KO+TAC than in WT+TAC. LV weight and lung weight/body weight were significantly lower in KO+TAC than in WT+TAC. No such changes were observed in either WT+Sham or KO+Sham. In parallel, myocyte cross-sectional area and collagen volume fraction were greater in KO+TAC than in WT+TAC. Interleukin-10 (IL-10) mRNA expression was completely abolished in KO+TAC compared to TAC.
Conclusions The disruption of NKT cell exacerbated the development of HF after TAC through the diminished expression of cardioprotective cytokine, IL-10. NKT cells play a critical role in the development of pressure-overload hypertrophy and failure.
- © 2011 by American Heart Association, Inc.