Pravastatin alleviates intracellular calcium dysregulation induced by Interleukin-6 via the mitochondrial ROS pathway in adult ventricular myocytes

Acute inflammation often contributes to the increased arrhythmogenesis in the cardiomyocytes. We investigated the protective effects of pravastatin on calcium disorders induced by acute administration of pro-inflammatory cytokines in isolated ventricular myocytes and its underlying mechanisms. Wild-type mice were intraperitoneally injected for five days with either pravastatin 20 mg/kg per day or an equal volume of normal saline. Cytosol Ca2+handling was studied in freshly isolated ventricular myocytes after acute exposure of interleukin-6 (IL-6) (1 ng/ml) for 120 min by Ionoptix and confocal microscopy. Acute administration of clinically relevant concentrations of IL-6 disturbed calcium handling in ventricular myocytes, which presented as decreased amplitudes, prolonged decay times of Ca2+transients, and reduced sarcoplasmic reticulum (SR) calcium stores. The frequency of spontaneous Ca2+release, including calcium sparks and spontaneous calcium waves, was dramatically enhanced in the setting of IL-6. Notably, the pretreatment of pravastatin alleviated disturbed Ca2+cycling, reduced spontaneous Ca2+leakage induced by IL-6. Mitochondrial ROS pathway may constitute the underlying mechanism of the protective effects of pravastatin. Pravastatin protected the cardiomyocytes against calcium disorders induced by IL-6 via the mitochondrial ROS pathway, which suggests that pravastatin may represent a promising auxiliary therapeutic strategy for cardiac injury under acute inflammation.