The Disruption of Natural Killer T cell Exacerbates Cardiac Hypertrophy and Heart Failure Due to Pressure Overload in Mice

Background. Natural killer T (NKT) cells produce various inflammatory cytokines and orchestrate tissue inflammation. Our previous study demonstrated that the activation of NKT cells attenuated the development of heart failure (HF) after myocardial infarction, which was mediated by the enhanced expression of interleukin-10 (IL-10). We, thus, hypothesized that the disruption of NKT cell could exacerbate cardiac hypertrophy and HF after pressure overload in mice. Methods and Results. Transverse aortic constriction (TAC) operation was performed in male C57BL/6J and NKT cell knockout (KO) mice. Sham, KO+sham, TAC, and KO+TAC were studied. Survival during 28 days was significantly lower in KO+TAC versus TAC (61% vs. 16%; P<0.05). Gene expressions of NKT cells receptors were increased by 60% in left ventricle (LV) from TAC compared to Sham at 14days. Echocardiography at 14days showed exaggerated LV hypertrophy with LV dilation and LV dysfunction in KO+TAC compared to TAC. Lung weight/body weight was significantly increased in KO+TAC compared to TAC. The myocyte cross-sectional area and collagen volume fraction were greater in KO+TAC than TAC. Interestingly, in parallel to the disruption of NKT cell, IL-10 mRNA expression was 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 IL-10. NKT cells play a critical role in the transition from hypertrophy to HF.