Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice

The increased cases of hyperlipemia in China and the crucial role of PM2.5 in inducing and promoting cardiovascular diseases have attracting more and more researchers’ attention. However, the effects and mechanisms of PM2.5 on cardiovascular system of hyperlipidemia people are still unclear. In this study, hyperlipidemia mice model was established by high-fat diet. Then we exposed these mice to PM2.5 or saline to explore the underling mechanism of cardiac injury in hyperlipidemia mice. The hyperlipemia mice are more susceptible to heart damage caused by PM2.5 exposure. The participation of oxidative stress, cell apoptosis and Ca2+ related mechanism could be observed in this model. After NAC (N-acetyl-L-cysteine) treatment, the oxidative stress level induced by PM2.5 exposure significantly decreased in hyperlipemia mice. NAC effectively alleviated cardiac injury, improved the imbalance of calcium and attenuated apoptosis induced by PM2.5 exposure in hyperlipemia mice. The strong oxidative stress in hyperlipemia mice could lead to calcium homeostasis imbalance and activation of apoptosis-related pathways. This mechanism of PM2.5-induced myocardial injury was also verified in vitro. In our present study, we demonstrated the contribution of the PM2.5-ROS-Ryr2-Ca2+ axis in PM2.5-induced heart injury of hyperlipidemia mice, offering a potential therapeutical target for related pathology. •PM2.5-induced heart injury is more severe in hyperlipemia mice.•Oxidative stress contributes to the more severe heart injury in hyperlipemia mice.•PM2.5-induced oxidative stress activates Ryr2-Ca2+ and apoptosis to exacerbate heart injury.