Cytotoxicity induced by fine particulate matter (PM2.5) via mitochondria-mediated apoptosis pathway in human cardiomyocytes

Abstract

Although the strongly causal associations were between fine particulate matter (PM_2.5) and cardiovascular disease, the toxic effect and potential mechanism of PM_2.5 on heart was poorly understood. Thus, the aim of this study was to evaluate the cardiac toxicity of PM_2.5 exposure on human cardiomyocytes (AC16). The cell viability was decreased while the LDH release was increased in a dose-dependent way after AC16 exposed to PM_2.5. The reactive oxygen species (ROS) generation and production of malondialdehyde (MDA) were increased followed by the decreasing in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The damage of mitochondria was observed by ultra-structural analysis and MMP measurement. The apoptotic rate of AC16 were markedly elevated which was triggered by PM_2.5. In addition, the proteins involved in mitochondria- mediated apoptosis pathway were measured. The protein levels of Caspase-3, Caspase-9 and Bax were up-regulated while the anti-apoptotic protein, Bcl-2 was down-regulated after AC16 exposed to PM_2.5. In summary, our results demonstrated that mitochondria-mediated apoptosis pathway played a critical role in PM_2.5-induced myocardial cytotoxicity in AC16, which suggested that PM_2.5 may contribute to cardiac dysfunction.

Keywords: Cytotoxicity; Fine particulate matter; Human cardiomyocytes; Mitochondria-mediated apoptosis pathway.