Role of pyroptosis in normal cardiac response to calorie restriction and starvation.

ABSTRACT

AIMS: An unhealthy diet is a major risk factor for cardiac diseases. Most researches focus on high fat diet, little is known about the detrimental effects of starvation on heart. METHODS: Mice were fed 100%, 40% and 20% of ad libitum to mimic the situation of moderate and severe caloric restriction (CR). To further evaluate the different effect of CR and starvation on cardiomyocyte, AC16 cells were treated with different concentrations of serum or glucose. TUNEL staining was performed to evaluate DNA damage in AC16 cells. HE and Masson staining were performed to detect the morphology and degree of fibrosis in myocardium from mice. Immunohistochemical staining, immunofluorescence staining, western blot and real-time PCR were used to detect the protein and mRNA expression of caspase-1, IL-1ß and IL-18. RESULTS: CR and starvation decrease body weight of mice in a concentration dependent manner. The starvation group showed a remarkable myocardial fibrosis with no significant alteration between control and CR groups. CR inhibited the activation of caspase-1 as well as the expression of IL-1ß and IL-18. On the contrary, starvation plays completely opposite effects, which was in accordance with histological changes. Similarly, different levels of serum and glucose deprivation were used to mimic the effect of CR and starvation in vitro. Moderate level of serum and glucose deprivation exerts protective effect on AC16 cells through the inhibition of pyroptosis, whereas high level of serum and glucose deprivation induces cell injury through the induction of pyroptosis. CONCLUSION: CR alleviates pyroptosis, whereas starvation promotes the progression of pyroptosis in myocardial tissues and cells.