In recent years, the cardiovascular toxicity of urban fine particulate matter (PM2.5) has sparked significant alarm. Mitochondria produce 90% of ATP and make up 30% of the volume of cardiomyocytes. Thus knowledge of myocardial mitochondrial dysfunction due to PM2.5 exposure is essential for further cardiotoxic effects. Here, the mechanism of PM2.5-induced cardiac hypertrophy through calcium overload and mitochondrial dysfunction was investigated in vivo and in vitro. Male and female BALB/c mice were given 1.28, 5.5, and 11 mg PM2.5/kg bodyweight weekly through oropharyngeal inhalation for four weeks and were assigned to low, medium, and high dose groups, respectively. PM2.5-induced myocardial edema and cardiac hypertrophy were detected in the high-dose group. Mitochondria were scattered and ruptured with abnormal ultrastructural morphology. In vitro experiments on human cardiomyocyte AC16 showed that exposure to PM2.5 for 24 h caused opened mitochondrial permeability transition pore --leading to excessive calcium production, decreased mitochondrial membrane potential, weakened mitochondrial respiratory metabolism capacity, and decreased ATP production. Nevertheless, the administration of calcium chelator ameliorated the mitochondrial damage in the PM2.5-treated group. Our in vivo and in vitro results confirmed that calcium overload under PM2.5 exposure triggered mTOR/AKT/GSK-3β activation, leading to mitochondrial bioenergetics dysfunction and cardiac hypertrophy.
Keywords: Calcium signaling pathway; Cardiac hypertrophy; Fine particulate matter; Mitochondrial bioenergetics.
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