Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.

中文翻译：

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呼吸道暴露于聚苯乙烯纳米塑料后小鼠心脏毒性的多维评估

纳米塑料（NPs）可以通过塑料制品的降解释放到环境中，其在空气中的含量不容忽视。迄今为止，还没有研究关注呼吸暴露于纳米粒子引起的心脏损伤效应和潜在机制。在这里，我们系统地研究了通过吸入暴露的 40 nm 聚苯乙烯纳米塑料 (PS-NP) 对小鼠的心脏毒性。设置四种暴露浓度（0 µg/天、16 µg/天、40 µg/天和 100 µg/天）和三种暴露持续时间（1 周、4 周、12 周）以获得更全面的信息，并进行 RNA-seq揭示急性、亚急性和亚慢性暴露后心脏毒性的潜在机制。PS-NPs 以剂量依赖性和时间依赖性方式诱导心脏损伤。急性、亚急性和亚慢性暴露增加了损伤生物标志物和炎症的水平，并扰乱了氧化酶和抗氧化酶活性之间的平衡。亚急性和亚慢性暴露会抑制心脏收缩功能，并导致心脏结构和超微结构损伤。从机制上讲，急性暴露后会引发剧烈的炎症和免疫反应。此外，线粒体损伤引起的心肌能量代谢紊乱，尤其是TCA循环可能是PS-NPs亚急性和亚慢性暴露后引起心脏损伤的潜在机制。本研究从PS-NPs的积累、心脏功能评估、组织学观察、生物标志物检测和转录组学研究等多个维度评估了PS-NPs呼吸暴露引起的心脏毒性。PS-NPs以剂量依赖性和时间依赖性的方式导致心脏结构和功能损伤，PS-NPs引起的心肌线粒体损伤可能是其心脏毒性的潜在机制。