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In recent years, the cardiovascular toxicity of urban fine particulate matter (PM 2.5 ) 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 PM 2.5 exposure is essential for further cardiotoxic effects. Here, the mechanism of PM 2.5 -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 PM 2.5 /kg bodyweight weekly through oropharyngeal inhalation for four weeks and were assigned to low, medium, and high dose groups, respectively. PM 2.5 -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 PM 2.5 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 PM 2.5 -treated group. Our in vivo and in vitro results confirmed that calcium overload under PM 2.5 exposure triggered mTOR/AKT/GSK-3β activation, leading to mitochondrial bioenergetics dysfunction and cardiac hypertrophy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Airborne particulate matter (PM) has been linked to cardiovascular diseases, but the underlying mechanisms remain unclear, especially at realistic exposure levels. In this study, both male and female BALB/c mice were employed to assess vascular homeostasis following a standard urban particulate matter, PM SRM1648a, via oropharyngeal aspiration at three environmentally relevant concentrations. The tested indicators included histopathological observation and lipid deposition, as well as redox biology and inflammatory responses. Furthermore, endothelial monolayer, vascular cell apoptosis and subcellular function were assessed to decipher whether episodic PM SRM1648a exposure leads to vascular damage after multiple periods of treatment, including subacute (4 weeks) and subchronic (8 weeks) durations. As a result, PM aspiration caused thickening of airways, leukocytes infiltration and adhesion to alveoli, with the spot of particles engulfed by pulmonary macrophages. Meanwhile, it induced local and systemic oxidative stress and inflammation, but limited pathological changes were captured throughout aortic tissues after either subacute or subchronic treatment. Furthermore, even in the absence of aortic impairment, vascular cell equilibrium has been disturbed by the characteristics of endothelial monolayer disintegration and cell apoptosis. Mechanistically, PM SRM1648a activated molecular markers of ER stress (BIP) and mitochondrial dynamics (DRP1) at both transcriptional and translational levels, which were strongly correlated to ox-inflammation and could serve as early checkpoints of hazardous events. In summary, our data basically indicate that episodic exposure of BALB/c mice to PM SRM1648a exerts limited effects on vascular histopathological alterations, but induces vascular cell apoptosis and subcellular dysfunction, to which local and systemic redox biology and inflammation are probably correlated., (Copyright © 2021 Elsevier B.V. All rights reserved.)